Rag1

Summary

Gene Symbol: Rag1
Description: recombination activating gene 1
Alias: Rag-1, V(D)J recombination-activating protein 1, recombinase activating gene 1, recombination activating protein 1
Species: mouse

Top Publications

  1. ncbi The quantitative assessment of MHC II on thymic epithelium: implications in cortical thymocyte development
    Soo Jung Yang
    Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Int Immunol 18:729-39. 2006
  2. pmc Innate and adaptive interleukin-22 protects mice from inflammatory bowel disease
    Lauren A Zenewicz
    Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520 USA
    Immunity 29:947-57. 2008
  3. ncbi RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J recombination
    M A Oettinger
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142
    Science 248:1517-23. 1990
  4. doi Adaptive Foxp3+ regulatory T cell-dependent and -independent control of allergic inflammation
    Maria A Curotto de Lafaille
    Program of Molecular Pathogenesis, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA
    Immunity 29:114-26. 2008
  5. doi Enteric flora expands gut lamina propria CX3CR1+ dendritic cells supporting inflammatory immune responses under normal and inflammatory conditions
    Jan Hendrik Niess
    Department of Internal Medicine I, Ulm University, Ulm, Germany
    J Immunol 184:2026-37. 2010
  6. pmc Different B cell populations mediate early and late memory during an endogenous immune response
    Kathryn A Pape
    Department of Microbiology, Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA
    Science 331:1203-7. 2011
  7. pmc Interleukin 7 signaling in dendritic cells regulates the homeostatic proliferation and niche size of CD4+ T cells
    Martin Guimond
    Pediatric Oncology Branch, National Cancer Institute, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Immunol 10:149-57. 2009
  8. doi AID and RAG1 do not contribute to lymphomagenesis in Emu c-myc transgenic mice
    R M Nepal
    Department of Immunology, University of Toronto, Medical Sciences Building, Toronto, Canada
    Oncogene 27:4752-6. 2008
  9. pmc Regulation of hierarchical clustering and activation of innate immune cells by dendritic cells
    Suk Jo Kang
    Howard Hughes Medical Institute, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143 0795, USA
    Immunity 29:819-33. 2008
  10. pmc No requirement for V(D)J recombination in p53-deficient thymic lymphoma
    M J Liao
    Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill Medical School, Chapel Hill, North Carolina 27599, USA
    Mol Cell Biol 18:3495-501. 1998

Research Grants

Detail Information

Publications200 found, 100 shown here

  1. ncbi The quantitative assessment of MHC II on thymic epithelium: implications in cortical thymocyte development
    Soo Jung Yang
    Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Int Immunol 18:729-39. 2006
    ..We discuss possible mechanisms for positive selection by weak interactions in the presence of such preformed MHC II aggregate units in cTEC...
  2. pmc Innate and adaptive interleukin-22 protects mice from inflammatory bowel disease
    Lauren A Zenewicz
    Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520 USA
    Immunity 29:947-57. 2008
    ..In addition, IL-22 expression was differentially regulated between NK cell subsets. Thus, both the innate and adaptive immune responses have developed protective mechanisms to counteract the damaging effects of inflammation on tissues...
  3. ncbi RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J recombination
    M A Oettinger
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142
    Science 248:1517-23. 1990
    ..RAG-1 and RAG-2 might activate the expression of the V(D)J recombinase but, more likely, they directly participate in the recombination reaction...
  4. doi Adaptive Foxp3+ regulatory T cell-dependent and -independent control of allergic inflammation
    Maria A Curotto de Lafaille
    Program of Molecular Pathogenesis, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA
    Immunity 29:114-26. 2008
    ..Thus, whereas adaptive Foxp3(+) Treg cells regulate sensitization to allergens and the severity of chronic inflammation, IFN-gamma-producing cells can play a beneficial role in inflammatory conditions involving eosinophils...
  5. doi Enteric flora expands gut lamina propria CX3CR1+ dendritic cells supporting inflammatory immune responses under normal and inflammatory conditions
    Jan Hendrik Niess
    Department of Internal Medicine I, Ulm University, Ulm, Germany
    J Immunol 184:2026-37. 2010
    ..The local bacteria-driven accumulation of CX(3)CR1(+) DCs seems to support inflammatory immune responses...
  6. pmc Different B cell populations mediate early and late memory during an endogenous immune response
    Kathryn A Pape
    Department of Microbiology, Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA
    Science 331:1203-7. 2011
    ..Thus, we propose that memory relies on swIg(+) cells until they disappear and serum immunoglobulin falls to a low level, in which case memory resides with durable IgM(+) reserves...
  7. pmc Interleukin 7 signaling in dendritic cells regulates the homeostatic proliferation and niche size of CD4+ T cells
    Martin Guimond
    Pediatric Oncology Branch, National Cancer Institute, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Immunol 10:149-57. 2009
    ..Our results indicate that IL-7Ralpha(+) DCs are regulators of the peripheral CD4(+) T cell niche and that IL-7 signals in DCs prevent uncontrolled CD4(+) T cell population expansion in vivo...
  8. doi AID and RAG1 do not contribute to lymphomagenesis in Emu c-myc transgenic mice
    R M Nepal
    Department of Immunology, University of Toronto, Medical Sciences Building, Toronto, Canada
    Oncogene 27:4752-6. 2008
    DNA breaks caused by recombination-activating gene 1 (RAG1) and activation-induced cytidine deaminase (AID) induce c-myc/immunoglobulin (Ig) heavy chain chromosomal translocations and thereby stimulate lymphomagenesis...
  9. pmc Regulation of hierarchical clustering and activation of innate immune cells by dendritic cells
    Suk Jo Kang
    Howard Hughes Medical Institute, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143 0795, USA
    Immunity 29:819-33. 2008
    ..Thus, spatial organization of the immune response by DCs between 6 and 24 hr ensures functional activation of innate cells, which restricts pathogens before adaptive immunity is fully activated...
  10. pmc No requirement for V(D)J recombination in p53-deficient thymic lymphoma
    M J Liao
    Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill Medical School, Chapel Hill, North Carolina 27599, USA
    Mol Cell Biol 18:3495-501. 1998
    ....
  11. pmc The BCL2A1 gene as a pre-T cell receptor-induced regulator of thymocyte survival
    Malay Mandal
    Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL 60637, USA
    J Exp Med 201:603-14. 2005
    ..Finally, we suggest that pre-TCR-induced A1 overexpression can contribute to T cell leukemia in both mice and humans...
  12. ncbi Autoreactive B cell responses to RNA-related antigens due to TLR7 gene duplication
    Prapaporn Pisitkun
    Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases NIAID, NIH, Rockville, MD 20852, USA
    Science 312:1669-72. 2006
    ..These results reveal high divergence in mouse Y chromosomes and represent a good example of gene copy number qualitatively altering a polygenic disease manifestation...
  13. pmc 53BP1 facilitates long-range DNA end-joining during V(D)J recombination
    Simone Difilippantonio
    Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892 1360, USA
    Nature 456:529-33. 2008
    ..These data suggest a more general role for 53BP1 in maintaining genomic stability during long-range joining of DNA breaks...
  14. pmc Mechanisms of tolerance induction in major histocompatibility complex class II-restricted T cells specific for a blood-borne self-antigen
    T Zal
    Department of Molecular Immunology, National Institute for Medical Research, Mill Hill, London, United Kingdom
    J Exp Med 180:2089-99. 1994
    ..When crossed onto a Rag1-/- background to prevent endogenous T cell receptor rearrangements, these peripheral potentially autoreactive cells ..
  15. ncbi The recombination activating gene-1 (RAG-1) transcript is present in the murine central nervous system
    J J Chun
    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142
    Cell 64:189-200. 1991
    ..The results suggest that RAG-1 functions in neurons, where its role might be to recombine elements of the neuronal genome site-specifically, or to prevent detrimental alterations of the genome in these long-lived cells...
  16. ncbi Identification of two catalytic residues in RAG1 that define a single active site within the RAG1/RAG2 protein complex
    S D Fugmann
    Howard Hughes Medical Institute, Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Mol Cell 5:97-107. 2000
    During V(D)J recombination, the RAG1 and RAG2 proteins cooperate to catalyze a series of DNA bond breakage and strand transfer reactions...
  17. doi Transcriptional repressor BCL6 controls Th17 responses by controlling gene expression in both T cells and macrophages
    Arpita Mondal
    Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
    J Immunol 184:4123-32. 2010
    ..BCL6-deficient T cells transplanted into Rag1(-/-) mice produced wild-type levels of IL-17, indicating that, in vivo, BCL6-deficient T cells develop relatively ..
  18. pmc NLRP10 is a NOD-like receptor essential to initiate adaptive immunity by dendritic cells
    Stephanie C Eisenbarth
    Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Nature 484:510-3. 2012
    ....
  19. ncbi Onset of TCR-beta gene rearrangement and role of TCR-beta expression during CD3-CD4-CD8- thymocyte differentiation
    D I Godfrey
    DNAX Research Institute, Palo Alto, CA 94304
    J Immunol 152:4783-92. 1994
    ....
  20. pmc B lymphocytes induce the formation of follicular dendritic cell clusters in a lymphotoxin alpha-dependent fashion
    Y X Fu
    Department of Laboratory Medicine Pathology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Exp Med 187:1009-18. 1998
    ..Thus, B cells themselves provide an essential signal that induces and maintains the lymphoid microenvironment essential for GC formation and class-switched Ig responses...
  21. pmc Myelin oligodendrocyte glycoprotein-specific T cell receptor transgenic mice develop spontaneous autoimmune optic neuritis
    Estelle Bettelli
    Center for Neurologic Diseases, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    J Exp Med 197:1073-81. 2003
    ..These results demonstrate that clinical manifestations of CNS autoimmune disease will vary depending on the identity of the target autoantigen and that MOG-specific T cell responses are involved in the genesis of isolated optic neuritis...
  22. pmc Topical vitamin D3 and low-calcemic analogs induce thymic stromal lymphopoietin in mouse keratinocytes and trigger an atopic dermatitis
    Mei Li
    Institut de Génétique et de Biologie Moléculaire et Cellulaire and Institut Clinique de la Souris, BP10142, 67404 Illkirch Cedex, France
    Proc Natl Acad Sci U S A 103:11736-41. 2006
    ..We propose molecular mechanisms through which vitamin D3 and retinoic acid signalings could be involved in the pathogenesis of atopic diseases...
  23. ncbi The V(D)J recombination activating gene, RAG-1
    D G Schatz
    Whitehead Institute for Biomedical Research, Nine Cambridge Center, Massachusetts 02142
    Cell 59:1035-48. 1989
    ..RAG-1 may activate V(D)J recombination indirectly, or it may encode the V(D)J recombinase itself...
  24. pmc Swift entry of myelin-specific T lymphocytes into the central nervous system in spontaneous autoimmune encephalomyelitis
    Glaucia C Furtado
    Molecular Pathogenesis Program, Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA
    J Immunol 181:4648-55. 2008
    ..Taken together, our results suggest that peripheral activation of T cells in draining lymph nodes is an early event in the development of EAE, which paves the way for the initial burst of IFN-gamma-producing CD4(+) T cell into the CNS...
  25. ncbi Mutations in T-cell antigen receptor genes alpha and beta block thymocyte development at different stages
    P Mombaerts
    Howard Hughes Medical Institute, Center for Cancer Research, Cambridge, Massachusetts
    Nature 360:225-31. 1992
    ..TCR-alpha is irrelevant in these developmental processes. The development of gamma delta T cells does not depend on either TCR-alpha or TCR-beta...
  26. ncbi Novel role of the Ras cascade in memory B cell response
    Yoshimasa Takahashi
    Department of Immunology, National Institute of Infectious Diseases, Shinjuku, Tokyo, Japan
    Immunity 23:127-38. 2005
    ..Thus, our data suggest that upon antigen stimulation, memory B cells are susceptible to apoptosis but can be rescued via an antiapoptotic effect mediated through the Ras cascade...
  27. pmc The in vivo pattern of binding of RAG1 and RAG2 to antigen receptor loci
    Yanhong Ji
    Department of Immunobiology, Yale University School of Medicine, 300 Cedar Street, Box 208011, New Haven, CT 06520 8011, USA
    Cell 141:419-31. 2010
    The critical initial step in V(D)J recombination, binding of RAG1 and RAG2 to recombination signal sequences flanking antigen receptor V, D, and J gene segments, has not previously been characterized in vivo...
  28. pmc Arthritogenic self-reactive CD4+ T cells acquire an FR4hiCD73hi anergic state in the presence of Foxp3+ regulatory T cells
    Ryan J Martinez
    Department of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455, USA
    J Immunol 188:170-81. 2012
    ..This suggests that autoimmune arthritis develops in the setting of lymphopenia when Foxp3(+)CD4(+) regulatory T cells are insufficient to functionally inactivate all autoreactive CD4(+) T cells that encounter self-Ag...
  29. pmc A zinc site in the C-terminal domain of RAG1 is essential for DNA cleavage activity
    LORI M GWYN
    Department of Biochemistry and Molecular Biology, The University of Oklahoma Health Sciences Center, Oklahoma City, 73190, USA
    J Mol Biol 390:863-78. 2009
    The recombination-activating protein, RAG1, a key component of the V(D)J recombinase, binds multiple Zn(2+) ions in its catalytically required core region...
  30. ncbi Functional immunoglobulin transgenes guide ordered B-cell differentiation in Rag-1-deficient mice
    E Spanopoulou
    Rockefeller University, New York, New York
    Genes Dev 8:1030-42. 1994
    ..These data also support the hypothesis that Rag-1 directly participates in the V(D)J recombination process...
  31. ncbi RAG mutations in human B cell-negative SCID
    K Schwarz
    Section of Molecular Biology, University of Ulm, D 89070 Ulm, Germany
    Science 274:97-9. 1996
    ..Six of 14 B- SCID patients tested were found to carry a mutation of the recombinase activating gene 1 (RAG-1), RAG-2, or both...
  32. ncbi Suppression of IL7Ralpha transcription by IL-7 and other prosurvival cytokines: a novel mechanism for maximizing IL-7-dependent T cell survival
    Jung Hyun Park
    Experimental Immunology Branch, National Cancer Institute, Building 10 Room 4B36, Bethesda, Maryland 20892, USA
    Immunity 21:289-302. 2004
    ..We suggest that this homeostatic regulatory mechanism promotes survival of the maximum possible number of T cells for the amount of IL-7 available...
  33. ncbi TRAF6 is a T cell-intrinsic negative regulator required for the maintenance of immune homeostasis
    Carolyn G King
    Department of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, Philadelphia, Pennsylvania 19104, USA
    Nat Med 12:1088-92. 2006
    ..These data identify a previously unrecognized role for TRAF6 in the maintenance of peripheral tolerance, and suggest the presence of a T cell-intrinsic control mechanism to render responder T cells susceptible to tolerizing signals...
  34. doi Constitutive crosspresentation of tissue antigens by dendritic cells controls CD8+ T cell tolerance in vivo
    Nancy Luckashenak
    Institute for Immunology, Ludwig Maximilian University, 80336 Munich, Germany
    Immunity 28:521-32. 2008
    ..Thus, our data demonstrate the importance of crosstolerance induction by DCs as a vital instrument for controlling self-reactive T cells from the peripheral repertoire and preventing autoimmune disease...
  35. pmc RAG-1 and ATM coordinate monoallelic recombination and nuclear positioning of immunoglobulin loci
    Susannah L Hewitt
    Department of Pathology, New York University School of Medicine, New York, New York, USA
    Nat Immunol 10:655-64. 2009
    ..homologous immunoglobulin pairing was much lower in the absence of the RAG-1-RAG-2 recombinase and was restored in Rag1-/- developing B cells with a transgene expressing a RAG-1 active-site mutant that supported DNA binding but not ..
  36. pmc Impaired V(D)J recombination and lymphocyte development in core RAG1-expressing mice
    Darryll D Dudley
    Howard Hughes Medical Institute, The Children s Hospital, The Center for Blood Research, Harvard Medical School, Boston, MA 02115, USA
    J Exp Med 198:1439-50. 2003
    b>RAG1 and RAG2 are the lymphocyte-specific components of the V(D)J recombinase. In vitro analyses of RAG function have relied on soluble, highly truncated "core" RAG proteins...
  37. ncbi An activated lck transgene promotes thymocyte development in RAG-1 mutant mice
    P Mombaerts
    Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge 02139
    Immunity 1:261-7. 1994
    ..In addition, p56lck may be involved in the down-regulation of the putative pre-TCR on CD4+CD8+ thymocytes...
  38. ncbi Overexpression of Bcl-2 in transgenic mice decreases apoptosis and improves survival in sepsis
    R S Hotchkiss
    Department of Anesthesiology, Howard Hughes Medical Institute, Washington University School of Medicine, St Louis, MO 63110, USA
    J Immunol 162:4148-56. 1999
    ..We conclude that overexpression of Bcl-2 provides protection against cell death in sepsis. Lymphocyte death may be detrimental in sepsis by compromising host defense...
  39. pmc The RAG1 N-terminal domain is an E3 ubiquitin ligase
    Vyacheslav Yurchenko
    Department of Pathology, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    Genes Dev 17:581-5. 2003
    b>RAG1 and RAG2 initiate V(D)J recombination, which is the assembly of immunoglobulin and T cell receptor genes. The N-terminal region of RAG1 can be deleted, leaving an enzymatic "core" able to catalyze the complete reaction...
  40. ncbi IL-21 induces the functional maturation of murine NK cells
    Jason Brady
    The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
    J Immunol 172:2048-58. 2004
    ..These developmental changes suggested that IL-21 functions to induce the terminal differentiation of mouse NK cells, resulting in heightened NK cell-mediated cytotoxicity and immune surveillance...
  41. pmc Adaptive immune cells temper initial innate responses
    Kwang Dong Kim
    Center for Infection and Immunity and National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Da Tun Road, Chaoyang District, Beijing 100101, China
    Nat Med 13:1248-52. 2007
    ..Therefore, adaptive immune cells have an unexpected role in tempering initial innate responses...
  42. pmc A WW-like module in the RAG1 N-terminal domain contributes to previously unidentified protein-protein interactions
    Radhashree Maitra
    Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, 10461, USA
    Nucleic Acids Res 37:3301-9. 2009
    More than one-third of the RAG1 protein can be truncated from the N-terminus with only subtle effects on the products of V(D)J recombination in vitro or in a mouse...
  43. doi The RING domain of RAG1 ubiquitylates histone H3: a novel activity in chromatin-mediated regulation of V(D)J joining
    Ursula Grazini
    Department of Experimental Oncology, European Institute of Oncology, Milan 20141, Italy
    Mol Cell 37:282-93. 2010
    The RAG1 and RAG2 proteins are the only lymphoid-specific factors required to perform the first step of V(D)J recombination, DNA cleavage...
  44. pmc Expansion of immunoglobulin-secreting cells and defects in B cell tolerance in Rag-dependent immunodeficiency
    Jolan E Walter
    Division of Immunology and The Manton Center for Orphan Disease Research, Children s Hospital, Harvard Medical School, Boston, MA 02115, USA
    J Exp Med 207:1541-54. 2010
    ..We have studied a mut/mut mouse model of leaky SCID with a homozygous Rag1 S723C mutation that impairs, but does not abrogate, V(D)J recombination activity...
  45. pmc Long-term T cell memory requires the surface expression of self-peptide/major histocompatibility complex molecules
    M A Markiewicz
    Gwen Knapp Center for Lupus and Immunology Research, The University of Chicago, Chicago, IL 60637, USA
    Proc Natl Acad Sci U S A 95:3065-70. 1998
    ..These data suggest that positive selection plays a role not only in T cell development but also in the maintenance of T cell memory...
  46. ncbi Rejection of H-Y disparate skin grafts by monospecific CD4+ Th1 and Th2 cells: no requirement for CD8+ T cells or B cells
    D Zelenika
    Therapeutic Immunology Group, Sir William Dunn School of Pathology, Oxford, United Kingdom
    J Immunol 161:1868-74. 1998
    ..Surprisingly, the transfer of either Th1 or Th2 CD4+ T cell lines from these mice into T cell-depleted recipients was sufficient to cause a specific rejection of male skin...
  47. pmc Lymphotoxin alpha/beta and tumor necrosis factor are required for stromal cell expression of homing chemokines in B and T cell areas of the spleen
    V N Ngo
    Department of Microbiology and Immunology, University of California San Francisco, San Francisco, California 94143, USA
    J Exp Med 189:403-12. 1999
    ..Together these findings indicate that LTalpha1beta2 and TNF are required for the development and function of B and T zone stromal cells that make chemokines necessary for lymphocyte compartmentalization in the spleen...
  48. ncbi Coordinate regulation of RAG1 and RAG2 by cell type-specific DNA elements 5' of RAG2
    W Yu
    Laboratory of Molecular Immunology, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
    Science 285:1080-4. 1999
    b>RAG1 and RAG2 are essential for V(D)J recombination and lymphocyte development. These genes are thought to encode a transposase derived from a mobile genetic element that was inserted into the vertebrate genome 450 million years ago...
  49. ncbi Following the development of a CD4 T cell response in vivo: from activation to memory formation
    S Garcia
    Division of Molecular Immunology, The National Institute for Medical Research, Mill Hill, London, United Kingdom
    Immunity 11:163-71. 1999
    ..They differ qualitatively from naive T cells, suggesting that accelerated CD4 memory responses can occur without the need for increased frequencies of specific T cells...
  50. pmc Mutational analysis of RAG1 and RAG2 identifies three catalytic amino acids in RAG1 critical for both cleavage steps of V(D)J recombination
    M A Landree
    Program in Cell and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    Genes Dev 13:3059-69. 1999
    b>RAG1 and RAG2 initiate V(D)J recombination, the process of rearranging the antigen-binding domain of immunoglobulins and T-cell receptors, by introducing site-specific double-strand breaks (DSB) in chromosomal DNA during lymphocyte ..
  51. pmc Mutations of acidic residues in RAG1 define the active site of the V(D)J recombinase
    D R Kim
    Molecular Biology Department, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    Genes Dev 13:3070-80. 1999
    The RAG1 and RAG2 proteins collaborate to initiate V(D)J recombination by binding recombination signal sequences (RSSs) and making a double-strand break between the RSS and adjacent coding DNA...
  52. ncbi Normal thymic architecture and negative selection are associated with Aire expression, the gene defective in the autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED)
    S Zuklys
    Pediatric Immunology, The Children s University Hospital, Basel University, Basel, Switzerland
    J Immunol 165:1976-83. 2000
    ..Aire may determine thymic stromal organization and with it the induction of self-tolerance...
  53. ncbi Differential survival of naive CD4 and CD8 T cells
    C Ferreira
    Division of Molecular Immunology, National Institute for Medical Research, London, United Kingdom
    J Immunol 165:3689-94. 2000
    ..However, expression levels of Bcl-2 in either transgenic or polyclonal naive CD4 and CD8 T cells are similar, excluding a role for this molecule as a key factor in differential survival of CD4 vs CD8 T cells...
  54. pmc The RAG proteins in V(D)J recombination: more than just a nuclease
    M J Sadofsky
    Medical College of Georgia, Institute of Molecular Medicine and Genetics, CB 2803, Augusta, GA 30912, USA
    Nucleic Acids Res 29:1399-409. 2001
    ..Two proteins, RAG1 and RAG2, together form the nuclease that cleaves the DNA at the border of the signal sequences...
  55. ncbi Increased accumulation of hybrid V(D)J joins in cells expressing truncated versus full-length RAGs
    J A Sekiguchi
    Howard Hughes Medical Institute, Harvard University Medical School, Boston, MA 02115, USA
    Mol Cell 8:1383-90. 2001
    b>RAG1 and RAG2 (RAGs) initiate V(D)J recombination by introducing breaks between two coding segments and flanking recombination signals (RSs). Nonhomologous end-joining (NHEJ) proteins then join the coding segments and join the RSs...
  56. ncbi Impairment of immunological memory in the absence of MHC despite survival of memory T cells
    George Kassiotis
    Division of Molecular Immunology, The National Institute for Medical Research, Mill Hill, London NW7 1AA, UK
    Nat Immunol 3:244-50. 2002
    ..Thus, in contrast to their survival, maintenance of the typical quality of memory T cells crucially depends on MHC-derived signals...
  57. pmc Mutational analysis of all conserved basic amino acids in RAG-1 reveals catalytic, step arrest, and joining-deficient mutants in the V(D)J recombinase
    Leslie E Huye
    Department of Immunolog, Baylor College of Medicine, Houston, Texas 77030, USA
    Mol Cell Biol 22:3460-73. 2002
    ..Our analysis of these mutants provides insights into the molecular mechanisms underlying these disorders...
  58. pmc Evidence of a critical architectural function for the RAG proteins in end processing, protection, and joining in V(D)J recombination
    Chia Lun Tsai
    Department of Molecular Biophysics and Biochemistry, Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    Genes Dev 16:1934-49. 2002
    ..We have identified RAG1 mutants that are proficient in DNA cleavage but defective in their ability to interact with coding ends after ..
  59. ncbi During the early prediabetic period in NOD mice, the pathogenic CD8(+) T-cell population comprises multiple antigenic specificities
    Teresa P DiLorenzo
    Department of Microbiology and Infectious Diseases, Faculty of Medicine, University of Calgary, Calgary, Alberta, T2N 4N1, Canada
    Clin Immunol 105:332-41. 2002
    ..NIT-1 cells represent an unlimited peptide source that will allow for the future isolation and sequencing of the novel multiple epitopes targeted early in the autoimmune response by pathogenic CD8(+) T cells...
  60. ncbi The resolution of relapsing fever borreliosis requires IgM and is concurrent with expansion of B1b lymphocytes
    Kishore R Alugupalli
    Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Immunol 170:3819-27. 2003
    ..hermsii. Together these results support the model that B1b cells generate the T-independent IgM required for the control and resolution of relapsing fever borreliosis...
  61. ncbi Immune complex-dependent remodeling of the airway vasculature in response to a chronic bacterial infection
    Arin B Aurora
    Department of Microbiology and Immunology, University of California, San Francisco, CA 94143, USA
    J Immunol 175:6319-26. 2005
    ..The results reveal a novel pathway whereby T cell-dependent humoral immunity to a persistent airway infection can induce inflammation-dependent angiogenesis, lymphangiogenesis, and chronic airway pathology...
  62. ncbi An intersection between the self-reactive regulatory and nonregulatory T cell receptor repertoires
    Chyi Song Hsieh
    Department of Medicine and Division of Rheumatology, University of Washington, Seattle, Washington 98195, USA
    Nat Immunol 7:401-10. 2006
    ..Our analyses suggest that T(reg) cells and potentially pathogenic autoimmune T cells use overlapping pools of self-reactive TCRs...
  63. pmc Interleukin 25 regulates type 2 cytokine-dependent immunity and limits chronic inflammation in the gastrointestinal tract
    Alexander M Owyang
    Department of Pathobiology, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Exp Med 203:843-9. 2006
    ..Therefore, IL-25 is not only a critical mediator of type 2 immunity, but is also required for the regulation of inflammation in the gastrointestinal tract...
  64. pmc Antigen-induced IL-10+ regulatory T cells are independent of CD25+ regulatory cells for their growth, differentiation, and function
    Kirsty S Nicolson
    Department of Cellular and Molecular Medicine, University of Bristol Medical School, University Walk, Bristol, United Kingdom
    J Immunol 176:5329-37. 2006
    ..These results demonstrate that these natural and induced regulatory cells fall into distinct subsets...
  65. pmc Lymphocyte recruitment into the aortic wall before and during development of atherosclerosis is partially L-selectin dependent
    Elena Galkina
    Department of Biomedical Engineering, University of Virginia, Health Sciences Center, Charlottesville, VA 22908, USA
    J Exp Med 203:1273-82. 2006
    ..Atherosclerosis induces the recruitment of macrophages and dendritic cells that support antigen presentation...
  66. pmc RANK signals from CD4(+)3(-) inducer cells regulate development of Aire-expressing epithelial cells in the thymic medulla
    Simona W Rossi
    Medical Research Council Centre for Immune Regulation, Institute for Biomedical Research, University of Birmingham, B15 2TT Birmingham, UK
    J Exp Med 204:1267-72. 2007
    ..Collectively, our data reveal cellular and molecular mechanisms leading to the generation of Aire(+) mTECs and highlight a previously unrecognized role for CD4(+)3(-)RANKL(+) inducer cells in intrathymic self-tolerance...
  67. pmc Survival of lethal poxvirus infection in mice depends on TLR9, and therapeutic vaccination provides protection
    Christofer Samuelsson
    Department of Research, Bavarian Nordic, Martinsried, Germany
    J Clin Invest 118:1776-84. 2008
    ..Therefore, these data suggest an essential role for TLR9 in the defense against poxviruses. In addition, postexposure application of MVA may protect against lethal poxvirus infection...
  68. ncbi High incidence of spontaneous autoimmune encephalomyelitis in immunodeficient anti-myelin basic protein T cell receptor transgenic mice
    J J Lafaille
    Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge 02139
    Cell 78:399-408. 1994
    ..The data also suggest that spontaneous EAE may be triggered by an in situ activation of CD4+ anti-MBP cells in the nervous system...
  69. ncbi A regulatory role for recombinase activating genes, RAG-1 and RAG-2, in T cell development
    J Wayne
    Howard Hughes Medical Institute, Rockefeller University, New York, New York 10021
    Immunity 1:95-107. 1994
    ..We propose that in addition to a previously documented role in V(D)J recombination, RAG-1 and RAG-2 expression must be properly regulated for completion of normal T cell development..
  70. ncbi Fyn can partially substitute for Lck in T lymphocyte development
    T Groves
    Division of Immunology and Cancer, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada
    Immunity 5:417-28. 1996
    ..These observations reveal that Fyn can subserve some Lck-like functions in T cell development...
  71. ncbi Definition of a large region of RAG1 that is important for coimmunoprecipitation of RAG2
    C J McMahan
    Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
    J Immunol 158:2202-10. 1997
    Interaction between the RAG1 and RAG2 proteins is probably critical for V(D)J recombination. Using a coimmunoprecipitation assay, we define a large region of RAG1 (amino acids 504-1008) that is sufficient for interaction with RAG2...
  72. ncbi Bcl-2 can rescue T lymphocyte development in interleukin-7 receptor-deficient mice but not in mutant rag-1-/- mice
    E Maraskovsky
    Department of Cellular Immunology, Immunex Research and Development Corporation, Seattle, Washington 98101, USA
    Cell 89:1011-9. 1997
    ..These results provide evidence that blocking apoptosis is the essential function of IL-7R during differentiation and activation of T lymphocytes and that pre-TCR signaling blocks a pathway to apoptosis that is insensitive to Bcl-2...
  73. ncbi Pre-TCR signaling and inactivation of p53 induces crucial cell survival pathways in pre-T cells
    M C Haks
    Division of Immunology, The Netherlands Cancer Institute, Amsterdam
    Immunity 11:91-101. 1999
    ..In addition, the CD4+ CD8+ (DP) compartment is expanded to its normal size. These findings suggest that the pre-TCR regulates progression through the DNA-damage checkpoint of the DN to DP transition by inactivating p53...
  74. ncbi Continued RAG expression in late stages of B cell development and no apparent re-induction after immunization
    W Yu
    Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10021, USA
    Nature 400:682-7. 1999
    ..Our findings may help to reconcile a series of apparently contradictory observations, and suggest a new model for the mechanisms that regulate allelic exclusion, receptor editing and tolerance...
  75. pmc The requirement of membrane lymphotoxin for the presence of dendritic cells in lymphoid tissues
    Q Wu
    Department of Pathology, The University of Chicago, Chicago, Illinois 60637, USA
    J Exp Med 190:629-38. 1999
    ..Taken together, these results support the notion that the signaling via LTbetaR by membrane LTalpha/beta is required for the presence of DCs in lymphoid tissues...
  76. ncbi Homeostasis and anergy of CD4(+)CD25(+) suppressor T cells in vivo
    Marc A Gavin
    Howard Hughes Medical Institute, University of Washington, Box 357370, Seattle, WA 98195, USA
    Nat Immunol 3:33-41. 2002
    ..DNA array analyses identified genes that may inhibit responsiveness at a number of levels in multiple signaling cascades in T(S) cells, as well as several anti-apoptotic genes that may mediate their survival...
  77. ncbi Transcription from the RAG1 locus marks the earliest lymphocyte progenitors in bone marrow
    Hideya Igarashi
    Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, 825 Northeast 13th Street, Oklahoma City 73104, USA
    Immunity 17:117-30. 2002
    Viable Lin(-) CD27(+) c-kit(Hi) Sca-1(Hi) GFP(+) cells recovered from heterozygous RAG1/GFP knockin mice progressed through previously defined stages of B, T, and NK cell lineage differentiation...
  78. pmc Spontaneous proliferation, a response of naive CD4 T cells determined by the diversity of the memory cell repertoire
    Booki Min
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 1892, USA
    Proc Natl Acad Sci U S A 101:3874-9. 2004
    ..This finding suggests that the immune system has evolved mechanisms to attain a memory cell repertoire of great diversity independently of foreign antigens...
  79. ncbi IFN-gamma determines distinct clinical outcomes in autoimmune encephalomyelitis
    Allen K Wensky
    Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine, New York University Medical Center, New York, NY 10016, USA
    J Immunol 174:1416-23. 2005
    ....
  80. pmc CD8+ T cell immunity against a tumor/self-antigen is augmented by CD4+ T helper cells and hindered by naturally occurring T regulatory cells
    Paul A Antony
    Division of Surgery, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 174:2591-601. 2005
    ..These findings reveal that Th cells can help break tolerance to a persisting self-Ag and treat established tumors through an IL-2-dependent mechanism, but requires simultaneous absence of naturally occurring T(reg) cells to be effective...
  81. ncbi Lineage-specific requirement for the PH domain of Vav1 in the activation of CD4+ but not CD8+ T cells
    Antonella Prisco
    Division of Immune Cell Biology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK
    Immunity 23:263-74. 2005
    ..Unexpectedly, the mutation selectively affects TCR-induced proliferation of CD4(+) but not CD8(+) T cells, demonstrating differences in the wiring of TCR signaling pathways between the two lineages...
  82. ncbi Transgenic insulin (B:9-23) T-cell receptor mice develop autoimmune diabetes dependent upon RAG genotype, H-2g7 homozygosity, and insulin 2 gene knockout
    Jean M Jasinski
    Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, P O Box 6511, MS B140, Aurora, CO 80045 6511, USA
    Diabetes 55:1978-84. 2006
    ..scid mouse. The current study demonstrates that the BDC12-4.1 TCR is sufficient to cause diabetes at NOD backcross 1, bypassing polygenic inhibition of insulitis and diabetogenesis...
  83. pmc Unique maturation program of the IgE response in vivo
    Agustin Erazo
    Program of Molecular Pathogenesis, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA
    Immunity 26:191-203. 2007
    ..Our results have implications for the understanding of IgE memory responses in allergy...
  84. pmc Mice lacking components of adaptive immunity show increased Brucella abortus virB mutant colonization
    Hortensia García Rolán
    Department of Medical Microbiology and Immunology, University of California, One Shields Avenue, Davis, CA 95616, USA
    Infect Immun 75:2965-73. 2007
    ..However, spleens of Rag1(-/-) mice and Igh6(-/-) mice were more highly colonized by the virB mutant than control mice after 14 to 21 days, ..
  85. ncbi Rag mutations reveal robust alternative end joining
    Barbara Corneo
    The Kimmel Center for Biology and Medicine of the Skirball Institute and Department of Pathology, New York University School of Medicine, New York, New York 10016, USA
    Nature 449:483-6. 2007
    ..mechanism for generating diversity in antigen receptors, relies on NHEJ for repairing DSBs introduced by the Rag1-Rag2 protein complex. Animals lacking any of the seven known NHEJ factors are therefore immunodeficient...
  86. pmc Tumor-specific Th17-polarized cells eradicate large established melanoma
    Pawel Muranski
    Center for Cancer Research, National Cancer Institute, National Institutes of Health, Mark O Hatfield Clinical Research Center, Bethesda, MD 20892, USA
    Blood 112:362-73. 2008
    ..This principle should be considered in designing clinical trials involving adoptive transfer-based immunotherapy of human malignancies...
  87. pmc Foxo1 directly regulates the transcription of recombination-activating genes during B cell development
    Rupesh H Amin
    Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720, USA
    Nat Immunol 9:613-22. 2008
    ..Foxo1 directly activated transcription of the Rag1-Rag2 locus throughout early B cell development, and a decrease in Foxo1 protein diminished the induction of Rag1 ..
  88. pmc TGF-beta signaling in dendritic cells is a prerequisite for the control of autoimmune encephalomyelitis
    Yasmina Laouar
    Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
    Proc Natl Acad Sci U S A 105:10865-70. 2008
    ..Our data provide direct evidence that TGF-beta can control autoimmunity via actions on DCs...
  89. pmc B lymphocyte activation by coinfection prevents immune control of friend virus infection
    Rute Marques
    Division of Immunoregulation, Medical Research Council National Institute for Medical Research, London, United Kingdom
    J Immunol 181:3432-40. 2008
    ..Thus, immune activation by coinfecting pathogens or their products can contribute to the pathogenicity of retroviral infection...
  90. pmc Plasminogen activator inhibitor-1 protects endothelial cells from FasL-mediated apoptosis
    Khalid Bajou
    Division of Hematology Oncology, Department of Pediatrics, University of Southern California and The Saban Research Institute of Childrens Hospital Los Angeles, Los Angeles, CA 90027, USA
    Cancer Cell 14:324-34. 2008
    ..We further demonstrate that plasmin cleaves FasL at Arg144-Lys145, releasing a soluble proapoptotic FasL fragment from the surface of ECs. The data provide a mechanism explaining the proangiogenic activity of PAI-1...
  91. pmc Soluble frizzled-related protein 1 is estrogen inducible in bone marrow stromal cells and suppresses the earliest events in lymphopoiesis
    Takafumi Yokota
    Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
    J Immunol 181:6061-72. 2008
    ..We now confirm with Rag1/GFP reporter mice that early lymphoid progenitors in the lineage marker(-) c-kit(high) ScaI(+), hematopoietic stem ..
  92. pmc West Nile virus-specific CD4 T cells exhibit direct antiviral cytokine secretion and cytotoxicity and are sufficient for antiviral protection
    James D Brien
    Department of Molecular Microbiology and Immunology, Oregon National Primate Research Center, Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR 97006, USA
    J Immunol 181:8568-75. 2008
    ..These results demonstrate the role of direct effector function of Ag-specific CD4 T cells in preventing severe WNV disease...
  93. pmc Leaky severe combined immunodeficiency and aberrant DNA rearrangements due to a hypomorphic RAG1 mutation
    William Giblin
    Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA
    Blood 113:2965-75. 2009
    The RAG1/2 endonuclease initiates programmed DNA rearrangements in progenitor lymphocytes by generating double-strand breaks at specific recombination signal sequences...
  94. pmc Structure of the RAG1 nonamer binding domain with DNA reveals a dimer that mediates DNA synapsis
    Fang Fang Yin
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA
    Nat Struct Mol Biol 16:499-508. 2009
    The products of recombination-activating genes RAG1 and RAG2 mediate the assembly of antigen receptor genes during lymphocyte development in a process known as V(D)J recombination...
  95. pmc Impaired lymphocyte development and antibody class switching and increased malignancy in a murine model of DNA ligase IV syndrome
    Anastasia Nijnik
    Henry Wellcome Building of Molecular Physiology, Oxford University, Oxford, United Kingdom
    J Clin Invest 119:1696-705. 2009
    ..These findings provide explanations for the complex lymphoid phenotype of human LigIV syndrome...
  96. pmc The receptor S1P1 overrides regulatory T cell-mediated immune suppression through Akt-mTOR
    Guangwei Liu
    Department of Immunology, St Jude Children s Research Hospital, Memphis, Tennessee, USA
    Nat Immunol 10:769-77. 2009
    ..Dynamic regulation of S1P1 contributed to lymphocyte priming and immune homeostasis. Thus, by antagonizing T(reg) cell-mediated immune suppression, the lipid-activated S1P1-Akt-mTOR pathway orchestrates adaptive immune responses...
  97. pmc Transcriptional repressor Blimp-1 promotes CD8(+) T cell terminal differentiation and represses the acquisition of central memory T cell properties
    Rachel L Rutishauser
    Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
    Immunity 31:296-308. 2009
    ..These results reveal a critical role for Blimp-1 in controlling terminal differentiation and suppressing memory cell developmental potential in effector CD8(+) T cells during viral infection...
  98. pmc Naive tumor-specific CD4(+) T cells differentiated in vivo eradicate established melanoma
    Ying Xie
    Program in Molecular Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
    J Exp Med 207:651-67. 2010
    ..Thus, these data provide a platform for designing immunotherapies that incorporate tumor/self-reactive CD4(+) T cells...
  99. pmc The RAG2 C terminus suppresses genomic instability and lymphomagenesis
    Ludovic Deriano
    Department of Pathology, New York University School of Medicine, New York, NY 10016, USA
    Nature 471:119-23. 2011
    Misrepair of DNA double-strand breaks produced by the V(D)J recombinase (the RAG1/RAG2 proteins) at immunoglobulin (Ig) and T cell receptor (Tcr) loci has been implicated in pathogenesis of lymphoid malignancies in humans and in mice...
  100. pmc The P4-type ATPase ATP11C is essential for B lymphopoiesis in adult bone marrow
    Owen M Siggs
    Department of Genetics, The Scripps Research Institute, La Jolla, California, USA
    Nat Immunol 12:434-40. 2011
    ..Our data establish an essential, cell-autonomous and context-sensitive function for ATP11C, a putative aminophospholipid flippase, in B cell development...
  101. pmc Silencing suppressor of cytokine signaling-1 (SOCS1) in macrophages improves Mycobacterium tuberculosis control in an interferon-gamma (IFN-gamma)-dependent manner
    Berit Carow
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm 17177, Sweden
    J Biol Chem 286:26873-87. 2011
    ..tuberculosis clearance early after infection in vivo in an IFN-γ-dependent manner. On the other hand, at later time points, SOCS1 expression by non-macrophage cells protected the host from infection-induced detrimental inflammation...

Research Grants32

  1. NEW MOUSE MODELS OF DIABESITY
    Edward Leiter; Fiscal Year: 2002
    ..Collectively, these studies will permit genetic and metabolic characterization of key events in the transition from simple obesity to diabesity in thee novel mouse models. ..
  2. New Insights into Animals Models of Diabetes
    Edward Leiter; Fiscal Year: 2003
    ..The meeting is planned for 200 participants. Because of limited seating capacity in The Jackson Laboratory's auditorium, the meeting venue will be the Bar Harbor Regency Hotel, where participants will be housed and fed. ..
  3. PATHOGENESIS OF AUTOIMMUNE DIABETES IN MICE
    Edward Leiter; Fiscal Year: 2004
    ..Understanding the contributions of diabetes modifying genes in the extended mouse MIHC may identify human HLA orthologs whose presence has recently been established. ..
  4. GENETICS AND PATHOLOGY OF NON-OBESE DIABETIC (NOD) MICE
    Edward Leiter; Fiscal Year: 2005
    ..These latter investigations are of particular importance in view of an ongoing NIDDK trial to prevent T1D in humans deemed at high risk by oral insulin treatment. ..
  5. Natural Killer Cell Mediated Control of Vaccinia Virus
    Anthony French; Fiscal Year: 2007
    ..The proposed work will occur under the mentorship of Dr. Wayne Yokoyama a recognized pioneer in the NK cell field who has successfully trained numerous graduate students and postdoctoral fellows. [unreadable] [unreadable]..
  6. Early T cell checkpoint violation in NOD mice
    Mary A Yui; Fiscal Year: 2010
    ..Identifying genes and pathways affectingT cells, which predispose NOD mice to T1D will help in the understanding of immune deviations that can lead to disease in humans. ..
  7. TNF Receptors of Colonic Epithelial Cells in IBD
    Emiko Mizoguchi; Fiscal Year: 2007
    ..Daniel K. Podolsky from the Division of Gastroenterology and by Dr. Atul K. Bhan from the Immunopathology Unit, both at Massachusetts General Hospital and Harvard Medical School. ..
  8. Regulatory Role of TNFR1 in Inflammatory Bowel Disease
    Emiko Mizoguchi; Fiscal Year: 2007
    ..We believe the data obtained from this study would provide an important rationale to develop new TNF related therapeutic approaches for human IBD. [unreadable] [unreadable] [unreadable]..
  9. Regulation of Osteoclast Differentiation by Pax5
    Mark Horowitz; Fiscal Year: 2007
    ..Such information would be applicable to a wide variety of skeletal defects including, post-menopausal osteoporosis, age-related osteopenia, fracture repair, and extended survival of prosthetic implants. ..
  10. CD8 T Cell Reactivity to IGRP as an Autoimmunity Marker in Type 1 Diabetes
    Teresa Dilorenzo; Fiscal Year: 2007
    ..Tests may also be developed to monitor destructive T cell activity in patients undergoing treatment, so that doctors will be able to know if the treatments are working. [unreadable] [unreadable] [unreadable]..
  11. SiRNA Gene Therapy for HIV/AIDS
    Ramesh Akkina; Fiscal Year: 2008
    ..4. Transduce siRNA constructs into the newly described CD34+/KDR+ primitive hematopoietic progenitor cells and derive macrophages in vitro and thymocytes in vivo, and evaluate their HIV-1 resistance. [unreadable] [unreadable]..
  12. REGULATION OF BONE REMODELING BY MEGAKARYOCYTES
    Mark Horowitz; Fiscal Year: 2009
    ..Such information would be applicable to a wide variety of skeletal defects including, post-menopausal osteoporosis, age-related osteopenia, fracture repair, and extended survival of prosthetic implants. ..
  13. Genomic dissection of platelet production
    Warren Alexander; Fiscal Year: 2009
    ....
  14. Immunological control of a persistent viral infection
    Sally R Sarawar; Fiscal Year: 2010
    ..The results obtained may have broader significance in understanding the mechanisms controlling T cell activation or tolerance, in general. ..
  15. ANALYSIS OF THE MURINE ANTIBODY REPERTOIRE
    GARNETT H KELSOE; Fiscal Year: 2010
    ..of B cells that initiatelsupport receptor editing;2) the role of self-antigens in the induction of regulated RAG 1/2 expression and rearrangement, and;3) the selection criteria that might determine clonal tolerance/selection ..
  16. CONTROL OF OSTEOGENESIS AND ADIPOGENESIS BY EBF
    Mark C Horowitz; Fiscal Year: 2010
    ..Such information would be applicable to a wide variety of skeletal defects including age-related osteopenia, post-menopausal osteoporosis, fracture repair, and extended survival of prosthetic implants. ..
  17. REGULATION OF HEMATOPOIESIS BY THROMBOPOIETIN
    Warren Alexander; Fiscal Year: 2001
    ..abstract_text> ..
  18. Mouse Models of Tumor Progression and Therapy Response
    CHRISTOPHER KEMP; Fiscal Year: 2007
    ..These experiments will reveal the molecular and cellular basis for the poor clinical outcome associated with p27 deficient tumors. This knowledge can then be applied to improve treatment design and regimen in the clinical setting. ..
  19. The antigen specificity of CD25+ CD4+ T regulatory cells
    CHYI HSIEH; Fiscal Year: 2005
    ..Understanding the antigen specificity of this important endogenous T cell suppressor may facilitate the development of disease specific treatments without broad immuno-suppressive side effects. ..
  20. Akt activation sustains silica induced inflammation
    CELINE BEAMER; Fiscal Year: 2006
    ..abstract_text> ..
  21. The Role of Double Strand Breaks in Carcinogenesis
    CHRISTOPHER KEMP; Fiscal Year: 2006
    ..Understanding the functional interaction of the P13 Ks, in regulating p53, apoptosis, development and carcinogenesis at the level of the whole animal is a necessary link to apply knowledge gained from cell culture models to the clinic. ..
  22. Modeling RNA-based HIV gene therapeutics in SCID-hu mice
    Ramesh Akkina; Fiscal Year: 2006
    ..4) Determine the engraftment and thymopoietic potential of lentivirally transduced primitive hematopoietic precursor cells i.e., a) CD34+ and KDR+ cells, b) SP cells in the SCID-hu mouse thymic microenvironment. ..
  23. B Cell Expansion After Dendritic Cell Immunization
    Michael Jordan; Fiscal Year: 2004
    ..My near term career path will involve ongoing basic research and study in order to improve my ultimate scientific productivity. ..
  24. Prevention of Diabetes with Lipid Immunomodulators
    Teresa Dilorenzo; Fiscal Year: 2005
    ....
  25. Role of BCL-6 in Allergic Immune Responses
    Alexander Dent; Fiscal Year: 2005
    ..These studies will also provide insight into the function of BCL6, which may help the treatment of B cell lymphoma. ..
  26. THE ROLE OF COMPLEMENT IN AUTOIMMUNITY
    Garnett Kelsoe; Fiscal Year: 2005
    ..Thus, we propose that the innate immune system controls both the frequency of peripheral, self-reactive B cells and their exposure to antigen. ..
  27. CHEMOKINES IN THE IMMUNE RESPONSE TO A VIRAL INFECTION
    Sally Sarawar; Fiscal Year: 2002
    ..3) The role of the CXCR2 chemokine receptor homologue in viral pathogenesis will be determined using a mutant virus in which the gene encoding the CXCR2 homologue has been inactivated. ..
  28. COMPLEMENT AND B CELL TOLERANCE IN A MURINE MODEL OF SLE
    Elahna Paul; Fiscal Year: 2002
    ..By combining immunologic, nephrologic and molecular analyses I propose to elucidate how classical complement deficiency predisposes to SLE. ..
  29. The stress of dry eye on corneal barrier function
    CINTIA DE PAIVA; Fiscal Year: 2006
    ..TJ and LEP expression will be evaluated by laser scanning confocal microscopy and immunostaining. Pro inflammatory mediator expression will be evaluated by Western Blot, ELISA and the Luminex Multiplex Assay. [unreadable] [unreadable]..
  30. Interaction between influenza virus and H. influenzae
    Sally Sarawar; Fiscal Year: 2007
    ..This could be particularly important during an influenza pandemic and may be more broadly applicable to other respiratory viruses. [unreadable] [unreadable] [unreadable]..
  31. Anti-Tumor Autoimmunity by lymphopenia T cell Expansion
    Roberto Baccala; Fiscal Year: 2008
    ..The results will define the role of homeostatic T cell proliferation in tumor autoimmunity, and provide new approaches to the treatment of cancer. [unreadable] [unreadable]..
  32. Gene expression in non-functional CD8 T cells
    Sally Sarawar; Fiscal Year: 2005
    ..The data are likely to lead to a new understanding of how CD8 T cells function in the control of persistent viral infections and mechanisms of CD8 T cell activation. ..