inbred mrl lpr mice

Summary

Summary: A mouse substrain that is genetically predisposed to the development of systemic lupus erythematosus-like syndrome, which has been found to be clinically similar to the human disease. It has been determined that this mouse strain carries a mutation in the fas gene. Also, the MRL/lpr is a useful model to study behavioral and cognitive deficits found in autoimmune diseases and the efficacy of immunosuppressive agents.

Top Publications

  1. ncbi Toll-like receptor 7 and TLR9 dictate autoantibody specificity and have opposing inflammatory and regulatory roles in a murine model of lupus
    Sean R Christensen
    Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    Immunity 25:417-28. 2006
  2. ncbi IL-10 regulates murine lupus
    Zhinan Yin
    Section of Rheumatology, Department of Medicine, Yale School of Medicine, New Haven, CT 06520, USA
    J Immunol 169:2148-55. 2002
  3. ncbi Inhibition of Toll-like receptor-7 (TLR-7) or TLR-7 plus TLR-9 attenuates glomerulonephritis and lung injury in experimental lupus
    Rahul D Pawar
    Medizinische Poliklinik, University of Munich, Pettenkoferstrasse 8a, 80336 Munich, Germany
    J Am Soc Nephrol 18:1721-31. 2007
  4. ncbi TCR/self-antigen interactions drive double-negative T cell peripheral expansion and differentiation into suppressor cells
    J J Priatel
    Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada
    J Immunol 167:6188-94. 2001
  5. ncbi Fas- and FasL-deficient mice are resistant to induction of autoimmune encephalomyelitis
    H Waldner
    Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 159:3100-3. 1997
  6. pmc The immune regulatory function of lymphoproliferative double negative T cells in vitro and in vivo
    Megan S Ford
    Department of Laboratory Medicine and Pathobiology, University of Toronto, Multi Organ Transplantation Program, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario M5G 2C4, Canada
    J Exp Med 196:261-7. 2002
  7. ncbi A new role for B cells in systemic autoimmunity: B cells promote spontaneous T cell activation in MRL-lpr/lpr mice
    O Chan
    Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520 8035, USA
    J Immunol 160:51-9. 1998
  8. ncbi Evidence for Fas-dependent and Fas-independent mechanisms in the pathogenesis of experimental autoimmune encephalomyelitis
    B N Dittel
    Section of Immunobiology, Yale University School of Medicine, Howard Hughes Medical Institute, New Haven, CT 06520, USA
    J Immunol 162:6392-400. 1999
  9. ncbi Genetic basis of murine lupus
    Marie Laure Santiago-Raber
    Department of Pathology, Centre Medical Universitaire, Geneva 4 1211, Switzerland
    Autoimmun Rev 3:33-9. 2004
  10. ncbi The proteasome inhibitor bortezomib depletes plasma cells and protects mice with lupus-like disease from nephritis
    Kirsten Neubert
    Interdisciplinary Center for Clinical Research, research group N2, Nikolaus Fiebiger Center of Molecular Medicine, University Hospital Erlangen, Glückstrasse 6, 91054 Erlangen, Germany
    Nat Med 14:748-55. 2008

Detail Information

Publications190 found, 100 shown here

  1. ncbi Toll-like receptor 7 and TLR9 dictate autoantibody specificity and have opposing inflammatory and regulatory roles in a murine model of lupus
    Sean R Christensen
    Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    Immunity 25:417-28. 2006
    ..These findings reveal opposing inflammatory and regulatory roles for TLR7 and TLR9, despite similar tissue expression and signaling pathways. These results have important implications for TLR-directed therapy of autoimmune disease...
  2. ncbi IL-10 regulates murine lupus
    Zhinan Yin
    Section of Rheumatology, Department of Medicine, Yale School of Medicine, New Haven, CT 06520, USA
    J Immunol 169:2148-55. 2002
    ..In summary, our results provide evidence that IL-10 can down-modulate murine lupus through inhibition of pathogenic Th1 cytokine responses. Modulation of the level of IL-10 may be of potential therapeutic benefit for human lupus...
  3. ncbi Inhibition of Toll-like receptor-7 (TLR-7) or TLR-7 plus TLR-9 attenuates glomerulonephritis and lung injury in experimental lupus
    Rahul D Pawar
    Medizinische Poliklinik, University of Munich, Pettenkoferstrasse 8a, 80336 Munich, Germany
    J Am Soc Nephrol 18:1721-31. 2007
    ..Hence, TLR-7 is proposed as a novel and potential therapeutic target in systemic lupus erythematosus...
  4. ncbi TCR/self-antigen interactions drive double-negative T cell peripheral expansion and differentiation into suppressor cells
    J J Priatel
    Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada
    J Immunol 167:6188-94. 2001
    ..Thus, the peripheral selection and maintenance of such autoreactive cells may serve to negatively regulate potential autoimmune T cell responses...
  5. ncbi Fas- and FasL-deficient mice are resistant to induction of autoimmune encephalomyelitis
    H Waldner
    Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 159:3100-3. 1997
    ..These results suggest that the Fas/FasL pathway plays a critical role in the development of EAE probably by mediating apoptosis within the target tissue...
  6. pmc The immune regulatory function of lymphoproliferative double negative T cells in vitro and in vivo
    Megan S Ford
    Department of Laboratory Medicine and Pathobiology, University of Toronto, Multi Organ Transplantation Program, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario M5G 2C4, Canada
    J Exp Med 196:261-7. 2002
    ..These findings clearly demonstrate that B6/lpr DNTC have a potent immune regulatory function in vitro and in vivo. They also provide new insights into the mechanisms involved in the development of autoimmune disease in lpr mice...
  7. ncbi A new role for B cells in systemic autoimmunity: B cells promote spontaneous T cell activation in MRL-lpr/lpr mice
    O Chan
    Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520 8035, USA
    J Immunol 160:51-9. 1998
    ..These results suggest a novel role for B cells in autoimmune disregulation...
  8. ncbi Evidence for Fas-dependent and Fas-independent mechanisms in the pathogenesis of experimental autoimmune encephalomyelitis
    B N Dittel
    Section of Immunobiology, Yale University School of Medicine, Howard Hughes Medical Institute, New Haven, CT 06520, USA
    J Immunol 162:6392-400. 1999
    ..Furthermore, transfer of cells lacking FasL (gld) into normal or gld recipients gave a diminished disease score. Thus, Fas/FasL interactions can play a role in the pathogenesis of EAE, but they are not required for disease to occur...
  9. ncbi Genetic basis of murine lupus
    Marie Laure Santiago-Raber
    Department of Pathology, Centre Medical Universitaire, Geneva 4 1211, Switzerland
    Autoimmun Rev 3:33-9. 2004
    ..Obviously, further identification of the genetic defects present in lupus-prone mice is of paramount importance for understanding the immunopathogenesis of SLE...
  10. ncbi The proteasome inhibitor bortezomib depletes plasma cells and protects mice with lupus-like disease from nephritis
    Kirsten Neubert
    Interdisciplinary Center for Clinical Research, research group N2, Nikolaus Fiebiger Center of Molecular Medicine, University Hospital Erlangen, Glückstrasse 6, 91054 Erlangen, Germany
    Nat Med 14:748-55. 2008
    ..Hence, the elimination of autoreactive plasma cells by proteasome inhibitors might represent a new treatment strategy for antibody-mediated diseases...
  11. ncbi Role of TLR9 in anti-nucleosome and anti-DNA antibody production in lpr mutation-induced murine lupus
    Aurelia Lartigue
    Institut National de la Santé et de la Recherche Médicale Unité 519 and Institut Fédératif de Recherche Multidisciplinaire sur les Peptides, Faculte de Medecine et Pharmacie, 22 Boulevard Gambetta, 76183 Rouen Cedex, France
    J Immunol 177:1349-54. 2006
    ..These results indicate that in C57BL/6-lpr/lpr mice, TLR9 is absolutely required for the anti-nucleosome Ab response but not for anti-dsDNA Ab production which is involved in mesangial proliferation...
  12. pmc RNA-associated autoantigens activate B cells by combined B cell antigen receptor/Toll-like receptor 7 engagement
    Christina M Lau
    Department of Microbiology, Boston University School of Medicine, MA 02118, USA
    J Exp Med 202:1171-7. 2005
    ..As further evidence that TLRs play a key role in autoantibody responses in SLE, we found that autoimmune-prone mice, lacking the TLR adaptor protein MyD88, had markedly reduced chromatin, Sm, and rheumatoid factor autoantibody titers...
  13. pmc Analysis of C4 and the C4 binding protein in the MRL/lpr mouse
    Scott E Wenderfer
    Center for Immunology and Autoimmune Diseases, Brown Foundation Institute of Molecular Medicine, 1825 Pressler Street, Houston, TX 77030, USA
    Arthritis Res Ther 9:R114. 2007
    ..Given that immune complex renal injury in the MRL/lpr mouse is independent of Fc receptors as well as the major negative regulator of the classical pathway, new mechanisms for immune-complex-mediated renal injury need to be considered...
  14. ncbi TCR ligation on CD8+ T cells creates double-negative cells in vivo
    W Z Mehal
    Section of Immunobiology, Yale University Medical School, New Haven, CT 06520 8011, USA
    J Immunol 161:1686-93. 1998
    ..CD95 is not essential for this process, because other mechanisms can compensate, but such mechanisms are less efficient in the LN...
  15. ncbi Paucity of V-D-D-J rearrangements and VH replacement events in lupus prone and nonautoimmune TdT-/- and TdT+/+ mice
    Lisa C Watson
    The Scripps Research Institute, Department of Immunology, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    J Immunol 177:1120-8. 2006
    ....
  16. ncbi Combined deficiency of proapoptotic regulators Bim and Fas results in the early onset of systemic autoimmunity
    Jack Hutcheson
    Department of Molecular Microbiology and Immunology, School of Medicine, Saint Louis University, Saint Louis, MO 63104, USA
    Immunity 28:206-17. 2008
    ..These data demonstrate that dysregulation of the Bcl-2 or Fas pathways can alter the function of APCs, thereby leading to SLE pathogenesis...
  17. ncbi Toll-like receptor 9 signaling protects against murine lupus
    Xiaobo Wu
    Washington University School of Medicine, St Louis, Missouri, USA
    Arthritis Rheum 54:336-42. 2006
    ..This study was undertaken to determine the role of TLR-9 in the MRL/+ and MRL/lpr models of murine lupus...
  18. ncbi Fc receptor-independent development of autoimmune glomerulonephritis in lupus-prone MRL/lpr mice
    Keiko Matsumoto
    Graduate School of Medicine, Chiba University, Chiba, Japan
    Arthritis Rheum 48:486-94. 2003
    ....
  19. ncbi Use of genetic knockouts to modulate disease expression in a murine model of lupus, MRL/lpr mice
    Christopher M Reilly
    Medical Research Service, Ralph H Johnson VAMC, Charleston, SC, USA
    Immunol Res 25:143-53. 2002
    ....
  20. ncbi Arthritis in MRL/lpr mice is under the control of multiple gene loci with an allelic combination derived from the original inbred strains
    Junji Kamogawa
    Ehime University School of Medicine, Shigenobu, Onsen gun, Ehime, Japan
    Arthritis Rheum 46:1067-74. 2002
    ..To clarify the mode of inheritance and the genome origins of arthritis in a lupus-prone strain of mice, MRL/MpJ, bearing a Fas deletion mutant gene, lpr (MRL/lpr)...
  21. ncbi Antagonist of interferon-inducible protein 10/CXCL10 ameliorates the progression of autoimmune sialadenitis in MRL/lpr mice
    Hitoshi Hasegawa
    First Department of Internal Medicine, Ehime University School of Medicine, Ehime, Japan
    Arthritis Rheum 54:1174-83. 2006
    ..We undertook the present study to investigate the expression of chemokines during the development of autoimmune sialadenitis in MRL/lpr mice and the therapeutic effect of chemokine antagonists on sialadenitis...
  22. ncbi T cell recognition and therapeutic effect of a phosphorylated synthetic peptide of the 70K snRNP protein administered in MR/lpr mice
    Fanny Monneaux
    Institut de Biologie Moléculaire et Cellulaire CNRS, UPR 9021, Strasbourg, France
    Eur J Immunol 33:287-96. 2003
    ..We further demonstrated that P140 is recognized by antibodies from lupus patients and binds to various HLA DR molecules, offering new hope for manipulating T cell response in humans...
  23. ncbi Toll-like receptors and activation of autoreactive B cells
    Elizabeth A Leadbetter
    Department of Microbiology, Boston University School of Medicine, Boston, Mass, USA
    Curr Dir Autoimmun 6:105-22. 2003
  24. ncbi Antagonist of monocyte chemoattractant protein 1 ameliorates the initiation and progression of lupus nephritis and renal vasculitis in MRL/lpr mice
    Hitoshi Hasegawa
    First Department of Internal Medicine, Ehime University School of Medicine, Shigenobu, Ehime, Japan
    Arthritis Rheum 48:2555-66. 2003
    ..To examine whether chemokine antagonists inhibit the initiation and progression of lupus nephritis in MRL/lpr mice...
  25. ncbi Chemokine expression precedes inflammatory cell infiltration and chemokine receptor and cytokine expression during the initiation of murine lupus nephritis
    G Perez de Lema
    Medizinische Poliklinik, Ludwig Maximilians Universitat, Pettenkoferstrasse 8a, D 80336 Munich, Germany
    J Am Soc Nephrol 12:1369-82. 2001
    ..These results support the hypothesis that chemokines initiate leukocyte infiltration and precede proteinuria and renal damage in MRL/lpr mice...
  26. ncbi Genomic view of systemic autoimmunity in MRLlpr mice
    J Liu
    Center for Immunology, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA
    Genes Immun 7:156-68. 2006
    ..These data provide a unique genomic view of the progression to fatal autoimmunity in MRLlpr mice, and provide new candidate genes and pathways to explore...
  27. ncbi Higher-order CpG-DNA stimulation reveals distinct activation requirements for marginal zone and follicular B cells in lupus mice
    Rachel Brummel
    Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
    Eur J Immunol 36:1951-62. 2006
    ..A corollary is that the heightened responsiveness of lupus B cells to TLR9-induced stimulation cannot be ascribed to unprimed follicular B cells, but is rather mediated by hypersensitive marginal zone B cells...
  28. ncbi Modulation of renal disease in MRL/lpr mice genetically deficient in the alternative complement pathway factor B
    H Watanabe
    Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA
    J Immunol 164:786-94. 2000
    ....
  29. ncbi Membranous glomerulonephritis development with Th2-type immune deviations in MRL/lpr mice deficient for IL-27 receptor (WSX-1)
    Sakiko Shimizu
    Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Maidashi, Fukuoka, Japan
    J Immunol 175:7185-92. 2005
    ..Loss of WSX-1 thus favors Th2-type autoimmune responses, suggesting that the Th1/Th2 balance may be a pivotal determinant of human lupus nephritis development...
  30. ncbi Genetic basis of autoimmune disease in MRL/lpr mice: dissection of the complex pathological manifestations and their susceptibility loci
    M Nose
    Department of Pathology Ehime, University School of Medicine, Japan
    Rev Immunogenet 2:154-64. 2000
    ..We conclude that the complex pathological manifestations of autoimmune disease are under the control of different combinations of polygenes...
  31. ncbi Anti-monocyte chemoattractant protein-1 gene therapy attenuates nephritis in MRL/lpr mice
    S Shimizu
    Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812 8582, Japan
    Rheumatology (Oxford) 43:1121-8. 2004
    ..The aim of this study was to examine whether anti-MCP-1 gene therapy inhibits the progression of nephritis in MRL/lpr mice...
  32. pmc Shutdown of an acute T cell immune response to viral infection is mediated by the proapoptotic Bcl-2 homology 3-only protein Bim
    Marc Pellegrini
    Division of Molecular Genetics of Cancer, The Walter and Eliza Hall Institute of Medical Research, Parkville 3050, Australia
    Proc Natl Acad Sci U S A 100:14175-80. 2003
    ..These findings have implications for the therapeutic manipulation of immune responses to infections and immunization...
  33. ncbi Antagonist of fractalkine (CX3CL1) delays the initiation and ameliorates the progression of lupus nephritis in MRL/lpr mice
    Atsushi Inoue
    Ehime University School of Medicine, Ehime, Japan
    Arthritis Rheum 52:1522-33. 2005
    ..Fractalkine (Fkn)/CX3CL1 and its receptor, CX3CR1, form one such chemokine system. We therefore undertook this study to investigate whether Fkn antagonist inhibits the initiation and progression of lupus nephritis in MRL/lpr mice...
  34. ncbi Activation of marginal zone B cells from lupus mice with type A(D) CpG-oligodeoxynucleotides
    Rachel Brummel
    Division of Rheumatology, Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
    J Immunol 174:2429-34. 2005
    ..Through increased IL-10 secretion, MZ-B cells may also modify the activity of other cell types, particularly dendritic cells and macrophages...
  35. ncbi Intramolecular T cell spreading in unprimed MRL/lpr mice: importance of the U1-70k protein sequence 131-151
    Fanny Monneaux
    Centre National de la Recherche Scientifique, Strasbourg, France
    Arthritis Rheum 50:3232-8. 2004
    ....
  36. pmc Loci predisposing to autoimmunity in MRL-Fas lpr and C57BL/6-Faslpr mice
    S Vidal
    Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Clin Invest 101:696-702. 1998
    ..The identification of loci with highly significant linkage to disease manifestations in Faslpr strains will make it possible to map and clone new genetic defects contributing to autoimmunity...
  37. ncbi Unique therapeutic effects of the Japanese-Chinese herbal medicine, Sairei-to, on Th1/Th2 cytokines balance of the autoimmunity of MRL/lpr mice
    Taisuke Ito
    Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan
    J Dermatol Sci 28:198-210. 2002
    ..On the other hand, Th2 cell type immunoglobulins (IgG1) were suppressed. These results suggested that Sairei-to is potential for impairing shifted Th1/Th2 balance and hypergammaglobulinemia resulting in therapeutic effects...
  38. ncbi C1q deficiency and autoimmunity: the effects of genetic background on disease expression
    Daniel A Mitchell
    Rheumatology Section, Division of Medicine, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London, UK W12 0NN
    J Immunol 168:2538-43. 2002
    ..The work also highlights the potential value of the C1q-deficient MRL/Mp(+/+) strain as a tool with which to dissect further the underlying mechanisms of the autoimmune syndrome associated with C1q deficiency...
  39. ncbi Immunological mechanisms and clinical implications of regulatory T cell deficiency in a systemic autoimmune disorder: roles of IL-2 versus IL-15
    Cui Hong Yang
    Department of Pathology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China
    Eur J Immunol 38:1664-76. 2008
    ..These findings thus provide a clear causal relationship and immunological mechanism underlying Treg deficiency and systemic autoimmunity...
  40. ncbi Mouse complement receptors type 1 (CR1;CD35) and type 2 (CR2;CD21): expression on normal B cell subpopulations and decreased levels during the development of autoimmunity in MRL/lpr mice
    K Takahashi
    Department of Pathology, University of Iowa School of Medicine, Iowa City 52242, USA
    J Immunol 159:1557-69. 1997
    ..We hypothesize that the early decrease in complement receptor expression such as that demonstrated by MRL/lpr mice plays an important role in the pathogenesis of murine and perhaps human SLE...
  41. pmc T cell-independent and toll-like receptor-dependent antigen-driven activation of autoreactive B cells
    Robin A Herlands
    Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520 8035, USA
    Immunity 29:249-60. 2008
    ..T cell-independent activation of certain autoreactive B cells, which gain stimuli via endogenous TLR ligands instead of T cells, may be the initial step in the generation of canonical autoantibodies...
  42. pmc Importance of spliceosomal RNP1 motif for intermolecular T-B cell spreading and tolerance restoration in lupus
    Fanny Monneaux
    Centre National de Recherche Scientifique UPR9021, Institut de Biologie Moleculaire et Cellulaire, 15 rue Rene Descartes, 67000 Strasbourg, France
    Arthritis Res Ther 9:R111. 2007
    ..The tolerogenic peptide P140, which is recognized by lupus patients' CD4+ T cells and known to protect MRL/lpr mice, is able to thwart emergence of intermolecular T-cell spreading in treated animals...
  43. ncbi Coordinate up-regulation of the beta-chemokine subfamily in autoimmune sialoadenitis of MRL/lpr mice
    W Mustafa
    Department of Periodontology, Faculty of Odontology, Huddinge University Hospital, Karolinska Institute, Stockholm, Sweden
    Scand J Immunol 48:623-8. 1998
    ..These observations implicate MCP-1, MIP-1beta and RANTES as potential chemokines in induction of MAS, and MCP-1, MIP-1beta, RANTES and prominently MIP-1alpha in progression and perturbation of MAS...
  44. pmc Identification of T-cell epitopes on U1A protein in MRL/lpr mice: double-negative T cells are the major responsive cells
    Mei Hui Yang
    Graduate Institute of Clinical Medicine Sciences, Chang Gung University, Taoyuan, Taiwan
    Immunology 115:279-86. 2005
    ..The study here provides information on T-cell epitope analysis of the U1A antigen using BM-DCs as the effective antigen-presenting cells...
  45. ncbi Murine models of systemic lupus erythematosus: B and T cell responses to spliceosomal ribonucleoproteins in MRL/Fas(lpr) and (NZB x NZW)F(1) lupus mice
    F Monneaux
    Institut de Biologie Moleculaire et Cellulaire, UPR 9021 Centre National de la Recherche Scientifique, 15 rue Rene Descartes, 6700 Strasbourg, France
    Int Immunol 13:1155-63. 2001
    ..This new finding can help to understand the mechanisms involved in the development of the anti-Sm/RNP antibody response and, particularly, the role played by non-MHC genes in this autoimmune response...
  46. ncbi Interleukin-18 receptor signaling is not required for autoantibody production and end-organ disease in murine lupus
    Ling Lin
    Washington University School of Medicine, St Louis, MO, USA
    Arthritis Rheum 52:984-6. 2005
  47. ncbi Clear suppression of Th1 responses but marginal amelioration of autoimmune manifestations by IL-12p40 transgene in MRL-FAS(lprcg)/FAS(lprcg) mice
    T Yasuda
    Laboratory Animal Research Center, University of Tokyo, Minato ku, Tokyo, Japan
    Cell Immunol 210:77-86. 2001
    ..The results suggest that excess p40 production in vivo may suppress Th1 responses in autoantibody and IFN-gamma production but lead to minimal improvement of clinical manifestations of autoimmune disease in this mouse model...
  48. ncbi Genetic determinants of autoimmune disease and coronary vasculitis in the MRL-lpr/lpr mouse model of systemic lupus erythematosus
    L Gu
    Department of Medicine, University of California, Los Angeles 90095, USA
    J Immunol 161:6999-7006. 1998
    ..Our results indicate that the QTLs on chromosomes 11 and 19 also control the development of vasculitis, demonstrating common genetic determinants of autoantibody levels and vasculitis...
  49. ncbi Enhanced lymphoproliferation and diminished autoimmunity in CD4-deficient MRL/lpr mice
    M S Chesnutt
    Department of Medicine, Department of Veterans Affairs Medical Center, San Francisco, California 94121, USA
    Clin Immunol Immunopathol 87:23-32. 1998
    ....
  50. ncbi Deficiency of 5-lipoxygenase abolishes sex-related survival differences in MRL-lpr/lpr mice
    J L Goulet
    Division of Nephrology, Department of Medicine, Duke University Medical Center, Durham, NC 27705, USA
    J Immunol 163:359-66. 1999
    ..These findings suggest that the presence of a functional 5lo gene confers a survival advantage on male MRL-lpr/lpr mice and that, when 5LO function is inhibited, either genetically or pharmacologically, this advantage is abolished...
  51. ncbi B cell anergy and systemic lupus erythematosus
    Su Jean Seo
    Wistar Institute, Philadelphia, PA, USA
    Curr Dir Autoimmun 6:1-20. 2003
  52. ncbi The centromeric region of chromosome 7 from MRL mice (Lmb3) is an epistatic modifier of Fas for autoimmune disease expression
    Philip L Kong
    Section of Rheumatology, Department of Internal Medicine, and Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
    J Immunol 172:2785-94. 2004
    ..Furthermore, they suggest that the genetic lesion(s) in MRLc7 is probably different from those in NZMc7 (Sle3/5), despite a significant overlap of these two intervals...
  53. ncbi The expression of plasma nucleosomes in mice undergoing in vivo apoptosis
    Ning Jiang
    Division of Rheumatology, Duke University Medical Center, Durham, NC 27709, USA
    Clin Immunol 106:139-47. 2003
    ..These results suggest that plasma nucleosome levels reflect specific patterns of cell death and are not an invariable consequence of in vivo apoptosis or immune cell activation...
  54. ncbi The emergence of anti-dsDNA antibodies precedes nucleosome-specific antibodies in MRL/lpr and MRL/+ mice
    Qing Lu
    Tokyo Medical and Dental University Graduate School of Allied Health Sciences, 1 5 45 Yushima, Bunkyo ku, Tokyo 113 8519, Japan
    J Med Dent Sci 50:9-15. 2003
    ....
  55. ncbi CD4+ T cells from (New Zealand Black x New Zealand White)F1 lupus mice and normal mice immunized against apoptotic nucleosomes recognize similar Th cell epitopes in the C terminus of histone H3
    Sylvie Fournel
    Institut de Biologie Moleculaire et Cellulaire, Unité Propre de Recherche 9021, Centre National de la Recherche Scientifique, and Université Louis Pasteur, Strasbourg, France
    J Immunol 171:636-44. 2003
    ..It might thus be important in the self-tolerance breakdown in lupus...
  56. ncbi Nrf2 deficiency improves autoimmune nephritis caused by the fas mutation lpr
    Naoki Morito
    Institute of Basic Medical Sciences, Institute of Clinical Medicine and Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba, Ibaraki, Japan
    Kidney Int 65:1703-13. 2004
    ..The result suggested that nrf2 is a possible candidate gene in determining susceptibility to autoimmune diseases. MRL/lpr mice, defective in Fas-mediated apoptosis, develop glomerulonephritis due to the production of autoantibodies...
  57. ncbi Type I IFN protects against murine lupus
    Jonathan D Hron
    Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    J Immunol 173:2134-42. 2004
    ....
  58. ncbi Role of the H-2 haplotype in Fas-intact lupus-prone MRL mice: association with autoantibodies but not renal disease
    Philip L Kong
    Yale University School of Medicine, New Haven, CT, USA
    Arthritis Rheum 48:2992-5. 2003
  59. ncbi Macrophages from lupus-prone MRL mice are characterized by abnormalities in Rho activity, cytoskeletal organization, and adhesiveness to extracellular matrix proteins
    Angelika Longacre
    Section of Nephrology, Department of Medicine, The University of Illinois at Chigaco, Chicago, IL 60612, USA
    J Leukoc Biol 76:971-84. 2004
    ....
  60. pmc A novel autoimmune pancreatitis model in MRL mice treated with polyinosinic:polycytidylic acid
    W M Qu
    Department of Pathology, Ehime University School of Medicine, Japan
    Clin Exp Immunol 129:27-34. 2002
    ..These findings suggest that an MRL strain of mice treated with poly I:C might be a good model for developing new approaches to the study of the pathogenesis of autoimmune pancreatitis...
  61. ncbi Increased plasma cell frequency and accumulation of abnormal syndecan-1plus T-cells in Igmu-deficient/lpr mice
    Jane Seagal
    Department of Immunology, Bruce Rappaport Faculty of Medicine, Technion Israel Institute of Technology, Haifa 31096, Israel
    Int Immunol 15:1045-52. 2003
    ..Our results, therefore, suggest that in the muMT/lpr mouse model a small population of isotype-switched B cells is sufficient for the initiation and propagation of Th1-regulated murine lupus...
  62. ncbi FcgammaRIIB deficiency with Fas mutation is sufficient for the development of systemic autoimmune disease
    Kaori Yajima
    Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan
    Eur J Immunol 33:1020-9. 2003
    ..Thus, Fc gamma RIIB deletion with Fas mutation is sufficient for the development of systemic autoimmunity in B6 mice. The inhibitory signaling cascade via Fc gamma RIIB may be critical for suppressing SLE in humans...
  63. pmc Genetic dissection of SLE: SLE1 and FAS impact alternate pathways leading to lymphoproliferative autoimmunity
    Xiaoyan Shi
    Simmon s Arthritis Research Center and the Center for Immunology, University of Texas Southwestern Medical School, Dallas 75235, USA
    J Exp Med 196:281-92. 2002
    ..Whereas FAS(lpr) functions as a recessive gene, Sle1 exhibits a gene dosage effect. These studies indicate that Sle1 and FAS(lpr) must be impacting alternate pathways leading to lymphoproliferative autoimmunity...
  64. ncbi Chemokine blockade for lupus model mice
    Hitoshi Hasegawa
    Department of Bioregulatory Medicine, Ehime University Graduate School of Medicine, Shitsukawa 454, Toon City, Ehime 791 0295, Japan
    Front Biosci 13:2900-8. 2008
    ..In this article, we review the role of chemokines and chemokine receptors involved in the pathogenesis of autoimmune diseases and the therapeutic approach of chemokine blockade in lupus model mice...
  65. ncbi Rheumatoid factors in health and disease: structure, function, induction and regulation
    Ann M Haberman
    Department of Laboratory Medicine, Section of Immunobiology, Yale University School of Medicine, New Haven, Conn, USA
    Curr Dir Autoimmun 6:169-95. 2003
  66. pmc IL-18 cDNA vaccination protects mice from spontaneous lupus-like autoimmune disease
    Paola Bossù
    Laboratory of Clinical and Behavioral Neurology, Istituto di Ricovero e Cura a Carattere Scientifico Fondazione Santa Lucia, 00179 Rome, Italy
    Proc Natl Acad Sci U S A 100:14181-6. 2003
    ..These studies support the concept that IL-18 plays a major role in the pathogenesis of the autoimmune syndrome of lpr mice and that a reduction in IL-18 activity could be a therapeutic strategy in autoimmune diseases...
  67. ncbi Costimulatory molecule-targeted antibody therapy of a spontaneous autoimmune disease
    Yonglian Sun
    Department of Pathology and Committee in Immunology, University of Chicago, Chicago, Illinois, USA
    Nat Med 8:1405-13. 2002
    ..This study demonstrates that agonistic monoclonal antibodies specific for costimulatory molecules can be used as novel therapeutic agents to delete autoreactive lymphocytes and block autoimmune disease progression...
  68. ncbi Tissue-specific expansion of NKT and CD5+B cells at the onset of autoimmune disease in (NZBxNZW)F1 mice
    Sufi Reza M Morshed
    Department of Immunology, Niigata University School of Medicine, Japan
    Eur J Immunol 32:2551-61. 2002
    ..Indeed, NKT cells in F(1) mice had a high potential to induce autoimmune-like inflammationwhen alpha-galactosylceramide was administered or when active NKT cells were transferred into young F(1) mice...
  69. ncbi Production and characterization of an anti-idiotypic single chain Fv that recognizes an anti-DNA antibody
    Myung Hee Kwon
    Department of Microbiology, Ajou University School of Medicine, Woncheon dong 5, Suwon 442 749, Korea
    Immunol Invest 31:205-18. 2002
    ..This characterized O2F3 scFv could be applied for the regulation of anti-DNA antibody production and the manipulation of recombinant antibody-based proteins to which toxins, enzymes, and chemical agents can be connected...
  70. ncbi Complement C4 is protective for lupus disease independent of C3
    Shirit Einav
    Center for Blood Research and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 168:1036-41. 2002
    ..Thus, complement C4 provides an important protective role against the development of SLE...
  71. pmc Differential roles of osteopontin/Eta-1 in early and late lpr disease
    G F Weber
    Department of Cancer Immunology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
    Clin Exp Immunol 126:578-83. 2001
    ..These observations define two stages of Fas(lpr/lpr) disease with respect to osteopontin-dependent pathogenesis that should be taken into account in the design of therapeutic approaches to the clinical disease...
  72. ncbi Lupus-prone mice have an abnormal response to thioglycolate and an impaired clearance of apoptotic cells
    Paul K Potter
    Rheumatology Section, Division of Medicine, Faculty of Medicine, Imperial College, Hammersmith Campus, London, United Kingdom
    J Immunol 170:3223-32. 2003
    ..These findings have implications for the initiation of autoimmunity, as lupus autoantigens are expressed on dying cells, and impaired disposal of these could enhance the development of autoimmunity...
  73. ncbi Terminal deoxynucleotidyl transferase deficiency decreases autoimmune disease in MRL-Fas(lpr) mice
    A J Feeney
    Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Immunol 167:3486-93. 2001
    ..Hence, either the T or B cell repertoires, or more likely both, require N region diversity to produce the full spectrum of autoimmune lupus disease...
  74. ncbi Carrier-dependent specificity of antibodies to a conserved peptide determinant of gp120
    S Karle
    Department of Pathology and Internal Medicine, Chemical Immunology and Therapeutics Research Center, University of Texas, Houston Medical School, Houston, TX 77030, USA
    Vaccine 21:1213-8. 2003
    ....
  75. pmc Programmed death ligand 1 regulates a critical checkpoint for autoimmune myocarditis and pneumonitis in MRL mice
    Julie A Lucas
    Laboratory of Molecular Autoimmune Disease, Renal Division, Harvard Medical School, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Immunol 181:2513-21. 2008
    ..Taken together, we suggest that PD-L1 expression is central to autoimmune heart and lung disease in lupus-susceptible (MRL) mice...
  76. ncbi Perforin protects against autoimmunity in lupus-prone mice
    S L Peng
    Department of Biology, Yale University, New Haven, CT 06510, USA
    J Immunol 160:652-60. 1998
    ....
  77. ncbi The role of noradrenergic nerves in the development of the lymphoproliferative disease in Fas-deficient, lpr/lpr mice
    Adriana del Rey
    Department of Immunophysiology, Institute of Physiology, Medical Faculty, Marburg, Germany
    J Immunol 176:7079-86. 2006
    ....
  78. ncbi Up-regulation of tubular epithelial interleukin-12 in autoimmune MRL-Fas(lpr) mice with renal injury
    X Fan
    Physiological Institute, University of Zurich Irchel, Switzerland
    Kidney Int 51:79-86. 1997
    ..In addition to mononuclear cells, TEC are an important source of IL-12 and could thereby participate in the development of a Th1 type immune response in autoimmune renal injury...
  79. ncbi The characteristics of hematopoietic stem cells from autoimmune-prone mice and the role of neural cell adhesion molecules in abnormal proliferation of these cells in MRL/lpr mice
    Xiaoli Wang
    First Department of Pathology, Kansai Medical University, 10 15 Fumizono cho, Moriguchi City, Osaka 570 8506, Japan
    Haematologica 92:300-7. 2007
    ..1 In order to understand how autoimmune diseases develop, we investigated the distinct qualitative differences between hematopoietic stem cells (HSC) from normal and autoimmune-prone mice...
  80. ncbi Abrogation of skin disease in LUPUS-prone MRL/FASlpr mice by means of a novel tylophorine analog
    Jin Young Choi
    Yale School of Medicine, Yale University, New Haven, Connecticut, USA
    Arthritis Rheum 54:3277-83. 2006
    ..To test the therapeutic effect of DCB-3503, a synthetic compound derived from a natural product that inhibits NF-kappaB, on end-organ disease in the MRL-Fas(lpr) murine model of systemic lupus erythematosus (SLE)...
  81. ncbi Role of MHC-linked genes in autoantigen selection and renal disease in a murine model of systemic lupus erythematosus
    Hideharu Sekine
    Department of Medicine, Division of Rheumatology and Immunology, Medical University of South Carolina and the Medical Research Service, Ralph H Johnson Veterans Affairs Medical Center, Charleston, SC 29425, USA
    J Immunol 177:7423-34. 2006
    ..These results indicate that genes encoded within or closely linked to the MHC region regulate autoantigen selection and isotype switching to IgG3 but have minimal effect on end-organ damage or survival in MRL/lpr mice...
  82. ncbi IL-21 has a pathogenic role in a lupus-prone mouse model and its blockade with IL-21R.Fc reduces disease progression
    Deborah Herber
    Inflammation, Wyeth Research, 200 Cambridge Park Drive, Cambridge, MA 02140, USA
    J Immunol 178:3822-30. 2007
    ..From a clinical standpoint, these results suggest that blocking IL-21 in systemic lupus erythematosus patients may represent a promising novel therapeutic approach...
  83. ncbi PI3K/AKT/mTOR hypersignaling in autoimmune lymphoproliferative disease engendered by the epistatic interplay of Sle1b and FASlpr
    Chun Xie
    Division of Rheumatology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Int Immunol 19:509-22. 2007
    ..Hence, hypersignaling via the PI3K/AKT/mTOR axis appears to be an important mechanism underlying autoimmune lymphoproliferative disease, presenting itself as a potential target for therapeutic intervention...
  84. ncbi Phase 2 enzyme induction by conjugated linoleic acid improves lupus-associated oxidative stress
    Paolo Bergamo
    Istituto di Scienze dell Alimentazione, Consiglio Nazionale delle Ricerche CNR ISA, Via Roma 52, 83100, Avellino, Italy
    Free Radic Biol Med 43:71-9. 2007
    ..In conclusion our data indicate that the activation of detoxifying enzymes may be one of the mechanisms whereby dietary CLA down-regulates oxidative stress in MRL/lpr mice...
  85. ncbi A genetic locus controlling aging-sensitive regression of B lymphopoiesis in an autoimmune-prone MRL/lpr strain of mice
    K Nakatani
    First Department of Internal Medicine, Nara Medical University, Kashihara, Japan
    Scand J Immunol 66:654-61. 2007
    ..This is first evidence for the presence of a genetic locus that affects B lymphopoiesis in an aging-sensitive manner...
  86. pmc Anti-chromatin antibodies drive in vivo antigen-specific activation and somatic hypermutation of rheumatoid factor B cells at extrafollicular sites
    Robin A Herlands
    Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520 8035, USA
    Eur J Immunol 37:3339-51. 2007
    ..This system provides a window on the initiation of an autoantibody response and reveals authentic initiators of it...
  87. ncbi Low-dose targeted complement inhibition protects against renal disease and other manifestations of autoimmune disease in MRL/lpr mice
    Carl Atkinson
    Department of Microbiology and Immunology and Children s Research Institute, Medical University ofSouth Carolina, Charleston 29425, USA
    J Immunol 180:1231-8. 2008
    ..Thus, targeted complement inhibition at the C3 level is an effective treatment in murine lupus, even beginning after onset of disease...
  88. pmc Tir8/Sigirr prevents murine lupus by suppressing the immunostimulatory effects of lupus autoantigens
    Maciej Lech
    Medical Policlinic, University of Munich, 80336 Munich, Germany
    J Exp Med 205:1879-88. 2008
    ..These data identify Sigirr as a novel SLE susceptibility gene in mice...
  89. ncbi Induction of immune-mediated hearing loss in SCID mice by injection of MRL/lpr mouse spleen cells
    H Iwai
    Department of Otorhinolaryngology, Kansai Medical University, Moriguchi, Osaka, Japan
    Hear Res 117:173-7. 1998
    ..These findings suggest that cell-mediated immunity is involved in the development of SHL and cochlear pathology...
  90. ncbi Resetting the epigenetic histone code in the MRL-lpr/lpr mouse model of lupus by histone deacetylase inhibition
    Benjamin A Garcia
    Department of Chemistry, University of Virginia, Charlottesville, Virginia 22904, USA
    J Proteome Res 4:2032-42. 2005
    ..These aberrant post-translational histone modifications can therefore be reset with histone deacetylase inhibition in vivo...
  91. ncbi Increased fetal and extramedullary hematopoiesis in Fas-deficient C57BL/6-lpr/lpr mice
    E Schneider
    Universite Rene Descartes Paris V, CNRS UMR 8603, Paris, France
    Blood 94:2613-21. 1999
    ..These data provide evidence that Fas deficiency can affect hematopoiesis both during adult and fetal life and that these modifications occur independently from other pathologies associated with the lpr phenotype...
  92. ncbi Polymorphisms in IgG Fc receptor IIB regulatory regions associated with autoimmune susceptibility
    Y Jiang
    Department of Pathology, Juntendo University School of Medicine, Tokyo, Japan
    Immunogenetics 51:429-35. 2000
    ..Our data imply that these FcgammaRIIB polymorphisms are selected evolutionarily for natural defense against pathogens, and that such polymorphisms may, in turn, form the basis of one aspect of autoimmune susceptibility...
  93. ncbi Fas and Fas ligand mutations inhibit autoantibody production in pristane-induced lupus
    M Satoh
    Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Florida, Gainesville, FL 32610, USA
    J Immunol 165:1036-43. 2000
    ..The data strongly support the idea that different subsets of autoantibodies are regulated differentially by cytokine stimulation and/or Fas signaling...
  94. ncbi B7 costimulation in the development of lupus: autoimmunity arises either in the absence of B7.1/B7.2 or in the presence of anti-b7.1/B7.2 blocking antibodies
    B Liang
    Department of Internal Medicine, Section of Rheumatology, Yale University School of Medicine, New Haven, CT 06510, USA
    J Immunol 163:2322-9. 1999
    ..These studies indicate that each B7 costimulatory signal may control unique pathological events in murine systemic lupus erythematosus that may not always be apparent in autoantibody titers alone...
  95. ncbi Islet-specific expression of IL-10 promotes diabetes in nonobese diabetic mice independent of Fas, perforin, TNF receptor-1, and TNF receptor-2 molecules
    B Balasa
    Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Immunol 165:2841-9. 2000
    ....
  96. ncbi IFN-gamma receptor signaling is essential for the initiation, acceleration, and destruction of autoimmune kidney disease in MRL-Fas(lpr) mice
    A Schwarting
    Renal Division, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Immunol 161:494-503. 1998
    ..In conclusion, IFN-gamma R signaling is essential for the initiation (CSF-1), acceleration (CSF-1 and TNF-alpha), and apoptotic destruction of renal parenchymal cells in MRL-Fas(lpr) autoimmune kidney disease...
  97. pmc MRL-lpr/lpr mice exhibit a defect in maintaining developmental arrest and follicular exclusion of anti-double-stranded DNA B cells
    L Mandik-Nayak
    The Wistar Institute, Philadelphia, Pennsylvania 19104, USA
    J Exp Med 189:1799-814. 1999
    ..Together, these data suggest that MRL mice are defective in maintaining the developmental arrest of autoreactive B cells and indicate a role for Fas in restricting entry into the follicle...
  98. ncbi Lymphocytes from autoimmune MRL lpr/lpr mice are hyperresponsive to IL-18 and overexpress the IL-18 receptor accessory chain
    D Neumann
    , L'Aquila, Italy
    J Immunol 166:3757-62. 2001
    ....
  99. pmc An epistatic effect of the female specific loci on the development of autoimmune vasculitis and antinuclear autoantibody in murine lupus
    M C Zhang
    Department of Pathology, Tohoku University Graduate School of Medicine, 2 1 Seiryo, Aoba ku, Sendai, Miyagi 980 8575, Japan
    Ann Rheum Dis 65:495-500. 2006
    ..To identify the genetic loci regulating the incidence and severity of renal autoimmune vasculitis developed in murine lupus...
  100. ncbi Expression and function of Fas on cells damaged by gamma-irradiation in B6 and B6/lpr mice
    J K Booker
    Department of Medicine, University of North Carolina, Chapel Hill 27599 7280, USA
    J Immunol 161:4536-41. 1998
    ..This study demonstrates that lpr mice can produce functional Fas protein. This system is also appropriate for identifying the in vivo role of Fas/FasL in apoptosis following other cell manipulations...
  101. ncbi Bone marrow transplantation: a new strategy for intractable diseases
    Susumu Ikehara
    First Department of Pathology, Transplantation Center, Regeneration Research Center for Intractable Diseases, Kansai Medical University, Moriguchi City, Osaka, Japan
    Drugs Today (Barc) 38:103-11. 2002
    ..since it can efficiently reconstitute the recipient with both donor-derived hemopoietic stem cells and mesenchymal stem cells...

Research Grants62

  1. Therapeutic Value of Fish Oil Rx on SLE and Bone Loss in Mice
    GABRIEL J J FERNANDES; Fiscal Year: 2012
    ..The proposed studies will also help to gain insight to undertake clinical studies to prevent renal and CVD as well as bone loss in SLE patients. ..
  2. TNF-like weak inducer of apoptosis (TWEAK) signaling in lupus nephritis
    Chaim Putterman; Fiscal Year: 2013
    ..Determine the effect of TWEAK signaling in resident kidney cells, and particularly podocytes, in the development of LN, including albuminuria and glomerulosclerosis. ..
  3. Role of reactive intermediates in lupus nephritis
    James C Oates; Fiscal Year: 2012
    ..The proposed research targeting these intermediates will potentially identify new biomarkers of disease and identify potential new targets for disease. ..
  4. Activation and regulation of autoreactive B cells in health and disease
    Mark J Shlomchik; Fiscal Year: 2012
    ..Since B cells are absolutely required for these diseases, and depleting them can induce remission in humans, this work is at the crux of understanding how autoimmune diseases like lupus occur and how to better treat them. ..
  5. TFE3 and TFEB in CD40L Dependent Murine Autoimmunity and Human Lupus
    CHRISTOPHER AJ ROMAN; Fiscal Year: 2010
    ..Such information is important to fully understand the molecular basis of this immune pathology, to devise new treatment strategies, and possibly identify new prognostic markers. ..
  6. Targeting CaMK4 in SLE
    George C Tsokos; Fiscal Year: 2013
    ..The significance of the proposed work lies with the fact that it presents a novel target for the treatment of SLE and that it develops a targeted delivery of a small drug. ..
  7. C3aR and C5aR Modulate T-cell Responses in the MRL Mouse
    Michael C Braun; Fiscal Year: 2010
    ..These studies are designed to advance our understanding of the mechanisms by which complement activation products modulate cellular immune responses and renal parenchymal responses in immune mediated renal injury. ..
  8. Molecular mechanisms of the impact of Fli-1 on lupus
    Xian Zhang; Fiscal Year: 2013
    ..This proposal will lead to a better understanding of the mechanisms of disease development and perhaps provide novel strategies for the treatment of disease. ..
  9. Role of PPARgamma signaling and adiponectin in Systemic Lupus Erythematosus
    Tamar Aprahamian; Fiscal Year: 2013
    ..The proposed research will enhance our understanding of the mechanisms underlying the therapeutic benefit of adiponectin and PPARg signaling in SLE and may lead to novel therapeutic approaches for the human disease. ..
  10. Regulation of Langerhans Cell Migration by Invariant Gamma Delta T Cells
    PETER JUNGHAN KIM; Fiscal Year: 2013
    ..Future studies will start to transition our studies of DETCs and LC migration to human samples. Better understanding of the factors regulating LC migration may lead to novel therapies for the control of lupus dermatitis. ..
  11. PATHOGENIC ROLE OF THE COMPLEMENT SYSTEM IN MURINE LUPUS
    Richard Quigg; Fiscal Year: 2009
    ..Specific manipulation of the complement system at each of the sites studied in this application is now possible and can be applied in a clinical setting if supported by work in the experimental animal. ..
  12. Inhibition of lupus nephritis in IRF-1 deficient mice
    Christopher Reilly; Fiscal Year: 2003
    ..Specific Aim 2: Study the in vivo effect of gene deletion of IRF-1 on MRL/lpr mice by backcrossing C57BL6 (IRF-1- /-) mice onto the MRL/lpr background. ..
  13. The Role of Recycling Immune Complexes in the Breakdown of Tolerance
    Barbara J Vilen; Fiscal Year: 2013
    ....
  14. Altered somatic mutation in IgAD/CVID; association with deficiency of Msh4/5
    Hideharu Sekine; Fiscal Year: 2009
    ..This line of investigation will provide new insight into the molecular basis of these immune deficiencies through novel mouse models that will rapidly translate into human disease. ..
  15. The role of Fli1 in the pathogenesis of lupus
    Tamara Nowling; Fiscal Year: 2009
    ..Results from these studies will be the foundation for future studies aimed at developing therapies for treating lupus patients. ..
  16. GENETIC CONTROL OF AUTOIMMUNITY
    Martin Weigert; Fiscal Year: 1999
    ..The etiology of autoantibodies in humans parallels that of the MRL/lpr. Thus the results of this proposal are of direct applicability to human disease. ..
  17. Nitric Oxide-Mediated Lacrimal Gland Damage in Sjogren's Syndrome
    Paul Brandt; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  18. MECHANISM OF AUTOREACTIVITY IN SLE
    Robert Eisenberg; Fiscal Year: 2001
    ..Is the pace of MRL/lpr disease dictated by events that occur after the early lymphocyte stage of ontogeny? 4. Does the genotype of the B cell control the lymphoproliferation of T cells? ..
  19. RECOMBINANT SINGLE DOMAIN & HYBRID PEPTIDASE ANTIBODIES
    Sudhir Paul; Fiscal Year: 2002
    ....
  20. Anti-Sm B-1 Cell Differentiation and Function
    Stephen Clarke; Fiscal Year: 2003
    ..In the final aim, the fate of B cells that normally differentiate to B-l will be determined in autoimmune MRL/lpr mice using a Tg model system of B-l differentiation. ..
  21. ROLE OF MURINE LEUKEMIA VIRUS IN AUTOIMMUNITY
    Seth Pincus; Fiscal Year: 2001
    ..The third aim is to correlate the expression of the antibody response to the retrovirus with the production of autoantibodies and to determine whether the anti-retrovirus antibodies are present in immune complexes from diseased kidneys. ..
  22. T-CELL CONTROL OF AUTOREACTIVITY IN SLE
    Philip Cohen; Fiscal Year: 2002
    ..Finally, unique anti-Sm transfected CH12 B lymphoma cells will be used as model APC to ask how Sm is processed, how it is presented to Sm-antigen specific T cells, and which APC are most efficient in Sm processing. ..
  23. The Role of Dendritic Cells and Macrophages in Systemic Lupus Erythematosus
    BARBARA VILEN; Fiscal Year: 2007
    ..To investigate if the loss of IL-6 and CD40L induce autoimmunity in non-autoimmune mice, we propose in aim 3b to monitor autoantibody production in IL-6"'" x CD40L"'" mice. ..
  24. A SERUM ASSAY FOR IN VIVO CYTOKINE PRODUCTION
    Fred Finkelman; Fiscal Year: 2000
    ..abstract_text> ..
  25. ANALYSIS OF IMMUNOREGULATORY DEFECT IN MRL/LPR MICE
    Ann Marshak Rothstein; Fiscal Year: 1991
    ....
  26. Mechanisms of autoreative B cell development in a lupus animal model
    Xian Zhang; Fiscal Year: 2009
    ..Our study will provide new insight into disease pathogenesis and understanding the development of autoimmune disease. These new findings will enable development of novel therapeutics that target the specific inflammation pathway ..
  27. BRAIN CELL DEATH IN MRL MICE: TARGETS AND MECHANISMS
    Boris Sakic; Fiscal Year: 2004
    ..abstract_text> ..
  28. Otitis Media Impact on the Inner Ear
    Dennis Trune; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  29. Roles of MIF and iNOS in SLE-associate inflammation
    Michael Hickey; Fiscal Year: 2007
    ..Using rMIF, anti-MIF mAb, and anti-MIF small molecules, and by generating MRL/Ipr/MIF -/- mice, we will examine the role of MIF in the modulation of leukocyte-endothelial interactions in murine SLE. [unreadable] [unreadable]..
  30. IMMUNOBIOLOGY AND GENETICS OF WOUND HEALING REGENERATION
    Ellen Heber Katz; Fiscal Year: 2001
    ....
  31. Mapping Murine Regeneation Genes
    ELLEN S HEBER KATZ; Fiscal Year: 2009
    ..Our study of regenerative healing using the well-defined LGXSM mouse resource enables us to realize the promising potential of this genetically powerful and unique healing model system. ..
  32. Histone deacetylases and atherosclerosis
    Nilamadhab Mishra; Fiscal Year: 2010
    ..Ultimately, this study may provide the foundation for the development of specific histone deacetylase inhibitors that only targets HDAC9 for the treatment of atherosclerosis in humans. ..
  33. ROLE OF PPAR GAMMA IN LUPUS NEPHRITIS
    Gary Gilkeson; Fiscal Year: 2005
    ..As agonists of PPAR gamma (the thiazolidinediones) are already approved for human use, insight gained from these studies can be quickly translated into human trials. ..
  34. Sex in Viral Myocarditis
    Sally Huber; Fiscal Year: 2004
    ..These studies may provide new insights as to how viruses affect developing host defense responses and how hormones can modulate this initial response. ..
  35. Mechanism of protection of DAF and CD59 in SLE
    Wenchao Song; Fiscal Year: 2009
    ..Such results should facilitate the development of innovative therapeutic strategies for human SLE. ..
  36. IMMUNOGENETIC AND CELLULAR ORIGINS OF NEPHROPHILIC ANAS
    Chandra Mohan; Fiscal Year: 2003
    ..NZMc1 mice that also bear the CD43++ knockout, or the lpr allele, for serological and clinical evidence of component lupus phenotypes. ..
  37. B CELL REPERTOIRE FORMATION
    ANN FEENEY; Fiscal Year: 2009
    ..Together, these studies should give insight into the epigenetic mechanisms and cis-elements which control VH gene rearrangement in fetal and adult pro-B cells. ..
  38. Heavy Metal-Induced Autoimmunity
    DWIGHT KONO; Fiscal Year: 2005
    ....
  39. Genetic Determinants of A. Fumigatus Susceptibility
    Aimee Zaas; Fiscal Year: 2008
    ..fumigatus infection, this proposal will identify and characterize genetic polymorphisms related to IA susceptibility in mice and validate these findings in a cohort of human bone marrow transplant donors and recipients. ..
  40. MERCURY INDUCED AUTOIMMUNITY
    Kenneth Pollard; Fiscal Year: 2007
    ..Identification of the role that IFN-gamma plays in the development of induced murine systemic autoimmunity should prove applicable to murine models of idiopathic systemic autoimmunity and to human lupus. ..
  41. B220+ DN alphabeta T cell as a novel immunoregulatory T*
    ABDEL HAMAD; Fiscal Year: 2005
    ..The findings generated by these studies will aid in characterizing a novel naturally occurring regulatory T cells and define their role in peripheral and mucosal tolerance. ..
  42. SPLENIC TOXICITY OF ANILINE
    M Firoze Khan; Fiscal Year: 2010
    ..These studies will elucidate the mechanisms of aniline-induced splenic toxicity, and will be important in devising strategies to prevent toxicity, and in risk assessment of aniline and other structurally-related aromatic amines. ..
  43. CD4+ T CELLS PROMOTE EARLY ATHEROSCLEROSIS
    Sally Huber; Fiscal Year: 2002
    ..Specific Aim 3 will investigate the role of CD4+ T cells in atherogenesis and evaluate whether these cells promote Th1 cell dominance. ..
  44. Impact of lupus susceptibility loci on B-cell tolerance
    Chandra Mohan; Fiscal Year: 2007
    ..Understanding how these loci/genes function will not only broaden our perspective of this disease, but will also point to potential targets for therapeutic intervention. ..
  45. Receptor Editing in Autoimmune and Normal Mice
    ANN FEENEY; Fiscal Year: 2009
    ..The information gained in these aims should give insights into the response of the various Ig loci to receptor editing signals, and how these processes may potentially be misregulated in B cells of autoimmune mice. ..
  46. Molecular Pharmacology of Estrogen Sulfotransferase
    Wenchao Song; Fiscal Year: 2006
    ..The proposed studies will provide a molecular basis for understanding the in vivo pharmacology and physiology of estrogen sulfotransferase as a prototypical phase II steroid sulfoconjugation enzyme. ..
  47. BECTON DICKINSON FACS CALIBUR 4 COLOR WITH SORT UNIT
    Kenneth Pollard; Fiscal Year: 2001
    ..Flow cytometry will be used to select and sort cell populations prior to and after transplantation studies. ..
  48. Lupus locus, Sle3- innate and adaptive immunity
    Chandra Mohan; Fiscal Year: 2005
    ..In particular, biochemical and genetic studies will be carried out to determine if S/e3 might impact the My D88 or TRIF dependent signaling pathways. ..
  49. Urine protein markers of disease in lupus nephritis
    James Oates; Fiscal Year: 2005
    ..Due to the power of proteomic and ANN techniques, novel mediators of disease activity and damage should be identified and thus contribute to the development of more targeted therapies for LN. ..
  50. Functional Analysis of Complement Receptor 2 as a Lupus Susceptibility Gene
    Susan A Boackle; Fiscal Year: 2010
    ....
  51. Cell Cycle Inhibition in Systemic Autoimmunity
    DWIGHT KONO; Fiscal Year: 2009
    ..These studies should yield important new insights into the significance and role of p21 in systemic autoimmunity and in host response to foreign antigens. ..
  52. Sex in Myocarditis
    Sally Huber; Fiscal Year: 2008
    ..By understanding the factors controlling virus infection and induction of innate immunity, better mechanism for controlling viral disease should be possible. ..
  53. Perfluorooctane sulfonate (PFOS) Affects Immunity through PPAR-alpha.
    Margie Peden Adams; Fiscal Year: 2007
    ..The unimmunized and immunized experiments will be conducted to control for possible differences in response related to lymphocyte activation from the immunization. [unreadable] [unreadable] [unreadable]..
  54. IMMUNOTOXICOLOGY OF A HEAVY METAL
    Kenneth Pollard; Fiscal Year: 2004
    ..Analysis of the interaction between fibrillarin, mercury and cells of the lymphoid system may lead to insights into how an imunotoxin renders self-antigen immunogenic. ..
  55. ROLE OF COMPLEMENT FACTOR B IN THE PATHOGENESIS OF SLE
    Gary Gilkeson; Fiscal Year: 2004
    ..These studies will provide new insight into the role of the alternative pathway in disease and potentially provide a new therapeutic target (Factor B) in immune complex mediated diseases. ..
  56. T reg Cells in Myocarditis
    Sally A Huber; Fiscal Year: 2010
    ..Determine whether the T reg cells are antigen specific (virus), cardiovascular specific (autoimmunity), or non-antigen specific. ..
  57. Impact of Fli-1 expression on lupus disease development
    Xian Zhang; Fiscal Year: 2007
    ..Aim 2. Identify molecular mechanisms whereby Fli-1 affects the response of the kidney in MRUIpr mice to inflammatory stimuli. Aim 3. Determine effect of reduced expression of Fli-1 on disease development in NZM2410 mice. ..
  58. XENOBIOTIC ACCELERATION OF AUTOIMMUNITY
    Kenneth Pollard; Fiscal Year: 2003
    ..abstract_text> ..
  59. CMV RETINITIS AND VIRAL RESISTANCE
    DOUGLAS JABS; Fiscal Year: 2003
    ....
  60. Role of nitric oxide and eicosanoids in lupus nepthritis
    James Oates; Fiscal Year: 2005
    ..In either event, future studies would address the use of selective COX-2 or TXA2 synthase inhibitors/receptor blockers, antioxidants, and/or PGI2/PGE2 agonists in conduction with iNOS inhibitors as therapies for LN. ..