Genomes and Genes
Gene Symbol: Stat4
Description: signal transducer and activator of transcription 4
Publications104 found, 100 shown here
- Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineagesLaurie E Harrington
Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA
Nat Immunol 6:1123-32. 2005..naive precursor cells to differentiate into T(H)-17 cells independently of the transcription factors STAT1, T-bet, STAT4 and STAT6...
- Generation of T follicular helper cells is mediated by interleukin-21 but independent of T helper 1, 2, or 17 cell lineagesRoza I Nurieva
Department of Immunology, University of Texas MD Anderson Cancer Center and Graduate School of Biomedical Sciences, Houston, TX 77030, USA
Immunity 29:138-49. 2008..This study thus demonstrates that Tfh is a distinct Th cell lineage...
- IL-1 family members and STAT activators induce cytokine production by Th2, Th17, and Th1 cellsLiying Guo
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Proc Natl Acad Sci U S A 106:13463-8. 2009..IL-17A in response to IL-1beta and a STAT3 activator and Th1 cells produce IFNgamma in response to IL-18 and a STAT4 inducer...
- Requirement for Stat4 in interleukin-12-mediated responses of natural killer and T cellsW E Thierfelder
Department of Biochemistry, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
Nature 382:171-4. 1996..b>Stat4 was initially cloned as a result of its homology with Stat1 (refs 4, 5) and is widely expressed, although it is ..
- IL-27 limits IL-2 production during Th1 differentiationAlejandro V Villarino
Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104, USA
J Immunol 176:237-47. 2006....
- The biology of Stat4 and Stat6A L Wurster
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, MA 02115, USA
Oncogene 19:2577-84. 2000..Stat6 and Stat4 are two STAT family members that specifically mediate signals that emanate from the IL-4 and IL-12 receptors, ..
- GATA-3 suppresses Th1 development by downregulation of Stat4 and not through effects on IL-12Rbeta2 chain or T-betTakashi Usui
Mucosal Immunity Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892, USA
Immunity 18:415-28. 2003To further understand the interaction among GATA-3, Stat4, and T-bet in helper T cell development, we first showed that retroviral expression of GATA-3 in developing Th1 cells suppresses Th1 development through downregulation of Stat4 ..
- Type I IFNs provide a third signal to CD8 T cells to stimulate clonal expansion and differentiationJulie M Curtsinger
Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA
J Immunol 174:4465-9. 2005..We show that IFN-alpha beta can provide the third signal directly to CD8 T cells via a STAT4-dependent pathway to stimulate survival, development of cytolytic function, and production of IFN-gamma...
- Role of Stat4-mediated signal transduction events in the generation of aggressor CD4+ T cells in herpetic stromal keratitis pathogenesisKaustuv Banerjee
Comparative and Experimental Medicine, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN 37916, USA
J Interferon Cytokine Res 27:65-75. 2007..involved in the development of aggressor CD4(+) T cells, ocular HSV infection was followed in mice deficient in Stat4 (Stat4(-/-) mice), the signal transducer for the cytokine interleukin-12 (IL-12)...
- SDF-1/CXCR4 mediates acute protection of cardiac function through myocardial STAT3 signaling following global ischemia/reperfusion injuryChunyan Huang
Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana, USA
Am J Physiol Heart Circ Physiol 301:H1496-505. 2011..Our results represent the first evidence that the SDF-1/CXCR4 axis upregualtes myocardial STAT3 activation and, thereby, mediates acute cardioprotection in response to global I/R...
- STAT4 is required for IFN-β-induced MCP-1 mRNA expression in murine mast cellsKazuma Iida
Department of Molecular Genetics, Graduate School of Medicine, Chiba University, Chiba, Japan
Int Arch Allergy Immunol 155:71-6. 2011..However, it is still largely unknown whether signal transducers and activators of transcription 4 (STAT4), one of the STAT proteins under type I IFN signaling, is involved in type I IFN-mediated gene expression in mast ..
- Coordinated and distinct roles for IFN-alpha beta, IL-12, and IL-15 regulation of NK cell responses to viral infectionKhuong B Nguyen
Deparment of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912, USA
J Immunol 169:4279-87. 2002..IL-12/STAT4 was critical for NK cell IFN-gamma expression, whereas IFN-alphabeta/STAT1 were required for induction of ..
- T-bet is a STAT1-induced regulator of IL-12R expression in naïve CD4+ T cellsMaryam Afkarian
Department of Pathology and Immunology, Howard Hughes Medical Institute, Washington University School of Medicine, Box 8118, 660 S Euclid Ave, St Louis, MO 63110, USA
Nat Immunol 3:549-57. 2002..through signal transducer and activator of transcription 1 (STAT1) and interleukin-12 (IL-12) signaling through STAT4 activation...
- Regulating type 1 IFN effects in CD8 T cells during viral infections: changing STAT4 and STAT1 expression for functionM Pilar Gil
Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02903, USA
Blood 120:3718-28. 2012..conditionally activate all of the signal transducers and activators of transcription molecules (STATs), including STAT4. The best-characterized signaling pathways use STAT1, however, and type 1 IFN inhibition of cell proliferation is ..
- Airway exposure levels of lipopolysaccharide determine type 1 versus type 2 experimental asthmaYoon Keun Kim
Department of Life Science, Postech Biotech Center, Pohang University of Science and Technology, Namgu, Pohang, Gyeongbuk, Republic of Korea
J Immunol 178:5375-82. 2007..mice, whereas the asthma phenotypes induced by high-dose LPS were abolished in the homozygous null mutation of the STAT4 gene...
- JAK/STAT signaling by cytokine receptorsK D Liu
Gladstone Institute of Virology and Immunology, San Francisco, California 94141, USA
Curr Opin Immunol 10:271-8. 1998..This signaling pathway influences normal cell survival and growth mechanisms and may contribute to oncogenic transformation...
- Modulation of chromatin structure regulates cytokine gene expression during T cell differentiationS Agarwal
Department of Pathology, Harvard Medical School, Center for Blood Research, Boston, Massachusetts 02115, USA
Immunity 9:765-75. 1998..We propose that chromatin remodeling of cytokine gene loci is functionally associated with productive T cell differentiation and may explain the coordinate regulation of Th2 cytokine genes...
- STAT-4 mediated IL-12 signaling pathway is critical for the development of protective immunity in cutaneous leishmaniasisL M Stamm
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, USA
Eur J Immunol 29:2524-9. 1999Recent studies have demonstrated that two IL-12 signaling pathways, a STAT 4 - dependent and STAT4 - independent, are involved in the development of a Th1-like response...
- STAT4 signal pathways regulate inflammation and airway physiology changes in allergic airway inflammation locally via alteration of chemokinesKavita Raman
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
J Immunol 170:3859-65. 2003Mice homozygous for the STAT4-null mutation were sensitized to cockroach Ag, challenged intratracheally 21 days later, and compared with STAT4-competent allergic mice...
- Regulation of IFN-gamma production by B effector 1 cells: essential roles for T-bet and the IFN-gamma receptorDavid P Harris
Trudeau Institute, Saranac Lake, NY 12983, USA
J Immunol 174:6781-90. 2005....
- Distinct requirements for the naturally occurring splice forms Stat4alpha and Stat4beta in IL-12 responsesTimothy Hoey
Tularik, Inc, South San Francisco, CA 94080, USA
EMBO J 22:4237-48. 2003..We have isolated an alternatively spliced isoform of Stat4, termed Stat4beta, which lacks 44 amino acids at the C-terminus, encompassing the putative transcriptional ..
- T helper type 1-specific Brg1 recruitment and remodeling of nucleosomes positioned at the IFN-gamma promoter are Stat4 dependentFuping Zhang
Department of Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
J Exp Med 203:1493-505. 2006..and positioned nucleosomes are remodeled, in a Th1-specific manner that is dependent on the transcription factor Stat4 and calcineurin phosphatase activity...
- Negative regulation of interleukin-12 signaling by suppressor of cytokine signaling-1Joanne L Eyles
The Walter and Eliza Hall Institute for Medical Research and The Cooperative Research Center for Cellular Growth Factors, PO Royal Melbourne Hospital, VIC 3050, Australia
J Biol Chem 277:43735-40. 2002..SOCS-1(-/-) disease, we generated mice lacking both SOCS-1 and signal transducer and activator of transcription 4 (STAT4), an essential component of the IL-12 signaling pathway...
- Microenvironment-dependent requirement of STAT4 for the induction of P-selectin ligands and effector cytokines on CD4+ T cells in healthy and parasite-infected miceUta Syrbe
Charite, Campus Mitte, Experimentelle Rheumatologie, c o Deutsches Rheumaforschungszentrum, Schumannstrasse 21 22, 10117 Berlin, Germany
J Immunol 177:7673-9. 2006..b>STAT4 is strongly involved in these processes...
- Synergy of IL-12 and IL-18 for IFN-gamma gene expression: IL-12-induced STAT4 contributes to IFN-gamma promoter activation by up-regulating the binding activity of IL-18-induced activator protein 1Masakiyo Nakahira
Department of Oncology, Osaka University Graduate School of Medicine, 2 2, Yamada oka, Suita, Osaka 565 0871, Japan
J Immunol 168:1146-53. 2002IL-12 and IL-18 synergistically enhance IFN-gamma mRNA transcription by activating STAT4 and AP-1, respectively. However, it is still unknown how STAT4/AP-1 elicit IFN-gamma promoter activation...
- The emerging role of T cell Ig mucin 1 in alloimmune responses in an experimental mouse transplant modelTakuya Ueno
Transplantation Research Center, Renal Division, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA
J Clin Invest 118:742-51. 2008..TIM-1-specific antibody treatment was more effective in Th1-type cytokine-deficient Stat4(-/-) recipients as compared with Th2-type cytokine-deficient Stat6(-/-) recipients...
- A crucial role for T-bet in selectin ligand expression in T helper 1 (Th1) cellsGreg H Underhill
Department of Microbiology Immunology, Feinberg School of Medicine, Northwestern University, 303 E Chicago Ave, Chicago, IL 60611, USA
Blood 106:3867-73. 2005..Further, we show that T-bet is responsible for the signal transducer and activator of transcription 4 (Stat4)-independent increase in Th1 cells of fucosyltransferase VII (FucT-VII)...
- Th2 cells are required for the Schistosoma mansoni egg-induced granulomatous responseM H Kaplan
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA
J Immunol 160:1850-6. 1998..mansoni ova in Stat4- and Stat6-deficient mice, which lack Th1 and Th2 cells, respectively...
- Inhibition of Th1 development mediated by GATA-3 through an IL-4-independent mechanismW Ouyang
Department of Pathology and Center for Immunology, Howard Hughes Medical Institute, Washington University School of Medicine, St Louis, Missouri 63110, USA
Immunity 9:745-55. 1998..Here, we show that loss of GATA-3 expression by developing Th1 cells requires IL-12 signaling through Stat4 and does not simply result from an absence of IL-4...
- Tyk2 negatively regulates adaptive Th1 immunity by mediating IL-10 signaling and promoting IFN-gamma-dependent IL-10 reactivationMichael H Shaw
Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02906, USA
J Immunol 176:7263-71. 2006..Thus, Tyk2 can be viewed as a dual-function Jak, mediating both pro and anti-inflammatory cytokine responses...
- Dendritic-cell maturation alters intracellular signaling networks, enabling differential effects of IFN-alpha/beta on antigen cross-presentationRandy S Longman
Rockefeller University, New York, NY, USA
Blood 109:1113-22. 2007..STAT1 in response to IFN-alpha/beta, whereas exposure of mature DCs to IFN-alpha/beta results in signaling via STAT4. Microarray analysis revealed numerous transcriptional changes resulting from the altered signaling...
- Disruption of the STAT4 signaling pathway protects from autoimmune diabetes while retaining antiviral immune competenceA Holz
Department of Neuropharmacology, Division of Virology, The Scripps Research Institute, La Jolla, CA 92037, USA
J Immunol 163:5374-82. 1999The role of the STAT4 signaling pathway in autoimmune diabetes was investigated using the rat insulin promoter lymphocytic choriomeningitis virus model of virally induced autoimmune diabetes...
- Transforming growth factor-beta1 enhances the interferon-gamma-dependent, interleukin-12-independent pathway of T helper 1 cell differentiationRonald B Smeltz
Laboratory of Immunology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Immunology 114:484-92. 2005..These data have important implications for strategies being considered for the use of TGF-beta-producing T cells for the treatment of autoimmune disorders...
- Helper T cell IL-2 production is limited by negative feedback and STAT-dependent cytokine signalsAlejandro V Villarino
Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104, USA
J Exp Med 204:65-71. 2007..by several signal transducer and activator of transcription (STAT) family transcription factors, namely STAT5, STAT4, and STAT6...
- Stat4 and Stat6 signaling in hepatic ischemia/reperfusion injury in mice: HO-1 dependence of Stat4 disruption-mediated cytoprotectionXiu Da Shen
Dumont UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, Los Angeles, CA 90095, USA
Hepatology 37:296-303. 2003..This study analyzes the role of signal transducer and activator of transcription 4 (Stat4) and Stat6 signaling in liver I/R injury...
- Increased susceptibility of Stat4-deficient and enhanced resistance in Stat6-deficient mice to infection with Trypanosoma cruziR L Tarleton
Department of Cellular Biology, University of Georgia, Athens, GA 30602, USA
J Immunol 165:1520-5. 2000..cruzi, mice with induced deficiencies in the Stat4 or Stat6 genes were infected with T. cruzi...
- Identification of STAT4-dependent and independent mechanisms of resistance to Toxoplasma gondiiG Cai
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
J Immunol 165:2619-27. 2000..To identify the transcription factors involved in this mechanism of resistance, mice deficient in STAT4, a protein involved in IL-12 signaling, were infected with T. gondii and their immune responses were analyzed...
- Stat3 and Stat4: members of the family of signal transducers and activators of transcriptionZ Zhong
Laboratory of Molecular Cell Biology, Rockefeller University, New York, NY 10021
Proc Natl Acad Sci U S A 91:4806-10. 1994..While Stat1 and Stat3 are widely expressed, Stat4 expression is restricted to testis, thymus, and spleen...
- Critical role for STAT4 activation by type 1 interferons in the interferon-gamma response to viral infectionKhuong B Nguyen
Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, RI 02912, USA
Science 297:2063-6. 2002..Here we show that IFN-alpha/beta activate STAT4 directly (STAT, signal transducers and activators of transcription) and that this is required for IFN-gamma ..
- Effector mechanisms of the autoimmune syndrome in the murine model of autoimmune polyglandular syndrome type 1Jason J DeVoss
Diabetes Center, University of California, San Francisco, CA 94143, USA
J Immunol 181:4072-9. 2008..Depletion of CD4(+) T cells using a neutralizing Ab ameliorated the disease process. Thus, therapies targeted specifically at the CD4(+) T cell subset may help control autoimmune disease in patients with APS1...
- High basal STAT4 balanced by STAT1 induction to control type 1 interferon effects in natural killer cellsTakuya Miyagi
Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912, USA
J Exp Med 204:2383-96. 2007..Regulation of their access to particular signaling pathways is poorly understood. STAT4 is important for IFN-gamma induction, and NK cells are major producers of this cytokine...
- Cutting edge: a murine, IL-12-independent pathway of IFN-gamma induction by gram-negative bacteria based on STAT4 activation by Type I IFN and IL-18 signalingMarina A Freudenberg
Max Planck Institut fur Immunbiologie, Freiburg, Germany
J Immunol 169:1665-8. 2002..pathway is based on a synergism of IFN-alphabeta and IL-18, and is independent of IL-12 signaling yet dependent on STAT4. In contradiction to current dogma, we show further that IFN-alphabeta alone induces tyrosine phosphorylation of ..
- Distinct characteristics of murine STAT4 activation in response to IL-12 and IFN-alphaLisa S Berenson
Department of Pathology and Center for Immunology, Washington University of School of Medicine, St Louis, MO 63110, USA
J Immunol 177:5195-203. 2006The role of type I IFN in Th1 development, STAT4 activation, and IFN-gamma production in murine T cells has remained unresolved despite extensive examination...
- Signal transducer and activator of transcription 4 is required for the transcription factor T-bet to promote T helper 1 cell-fate determinationVivian T Thieu
Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Immunity 29:679-90. 2008..The transcription factors signal tranducer and activator of transcription 4 (Stat4) and T-bet are required for the interleukin-12 (IL-12)-stimulated development of T helper 1 (Th1) cells, although ..
- Impaired IL-12 responses and enhanced development of Th2 cells in Stat4-deficient miceM H Kaplan
Department of Cancer Biology, Harvard School of Public Health, Boston, Massachusetts 02115, USA
Nature 382:174-7. 1996..b>STAT4 is one member of this family, and is activated only in response to the cytokine interleukin (IL)-12 (refs 5, 6)...
- A signal transducer and activator of transcription (Stat)4-independent pathway for the development of T helper type 1 cellsM H Kaplan
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA
J Exp Med 188:1191-6. 1998..We have generated mice lacking both Stat4 and Stat6 to examine the ability of Th cells to develop in the absence of these two transcription factors...
- A point mutation in the IL-12R beta 2 gene underlies the IL-12 unresponsiveness of Lps-defective C57BL/10ScCr miceA Poltorak
The Scripps Research Institute, La Jolla, CA 92037 Max Planck Institut für Immunbiologie, Freiburg, Germany
J Immunol 167:2106-11. 2001..phosphorylation of Janus kinase 2, but, unlike the wild-type IL-12R, can no longer mediate phosphorylation of STAT4. Because the phosphorylation of STAT4 is a prerequisite for the IL-12-mediated induction of IFN-gamma, its absence ..
- The transcription factor STAT5 is critical in dendritic cells for the development of TH2 but not TH1 responsesBryan D Bell
Immunology Program, Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA
Nat Immunol 14:364-71. 2013..Our results show that the TSLP-STAT5 axis in DCs is a critical component for the promotion of type 2 immunity at barrier surfaces...
- Unlike αβ T cells, γδ T cells, LTi cells and NKT cells do not require IRF4 for the production of IL-17A and IL-22Hartmann Raifer
Institut für Medizinische Mikrobiologie und Krankenhaushygiene, Philipps Universitat Marburg, Marburg, Germany
Eur J Immunol 42:3189-201. 2012..IL-17A-producing WT and Irf4(-/-) γδ T cells equally express CCR6 and lack CD27. The underlying IRF4-independent pathway partially involves STAT3 during in vitro stimulation...
- Spatial congregation of STAT binding directs selective nuclear architecture during T-cell functional differentiationOfir Hakim
Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Genome Res 23:462-72. 2013..Such subnuclear environments have significant implications for efficient functioning of the mature effector lymphocytes...
- STAT4 regulates antiviral gamma interferon responses and recurrent disease during herpes simplex virus 2 infectionAlexandra Svensson
Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
J Virol 86:9409-15. 2012b>STAT4 is an important transcription factor that contributes to the incidence and severity of different autoimmune diseases and is implicated in the antiviral immune responses in mice...
- STAT4 and T-bet are required for the plasticity of IFN-γ expression across Th2 ontogeny and influence changes in Ifng promoter DNA methylationChristopher L Williams
Department of Microbiology and Immunology, Vanderbilt University, Nashville TN 37232, USA
J Immunol 191:678-87. 2013..by a loss of the repressive DNA methylation of the Ifng promoter acquired during Th2 polarization yet requires STAT4 along with T-box expressed in T cells...
- Orally induced peripheral nonresponsiveness is maintained in the absence of functional Th1 or Th2 cellsH N Shi
Mucosal Immunology Laboratory, Massachusetts General Hospital, Charlestown 02129, USA
J Immunol 162:5143-8. 1999..In the mucosa, however, the absence of Th1 and Th2 cytokines can markedly affect this response, perhaps by regulation of TGF-beta-secreting cells...
- Cysteine protease B of Leishmania mexicana inhibits host Th1 responses and protective immunityLaurence U Buxbaum
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
J Immunol 171:3711-7. 2003..Lesion resolution was Th1 dependent, as Deltacpb-infected IL-12p40(-/-) and STAT4(-/-) mice developed high parasite burdens and progressive disease. Moreover, when L...
- Selective loss of type I interferon-induced STAT4 activation caused by a minisatellite insertion in mouse Stat2J D Farrar
Department of Pathology and Center for Immunology, Howard Hughes Medical Institute, Washington University School of Medicine, 660 S Euclid, St Louis, MO 63110, USA
Nat Immunol 1:65-9. 2000..immunity to direct the development of T helper subsets, for example toward subset 1 (TH1) development through STAT4 activation...
- IL-12 is required for anti-OX40-mediated CD4 T cell survivalCarl E Ruby
Earle A Chiles Research Institute, Providence Portland Medical Center, Portland, OR 97213, USA
J Immunol 180:2140-8. 2008..this window of IL-12Rbeta2 expression, was required for enhanced T cell survival and survival was associated with STAT4-specific signaling...
- Toll-like receptor and IL-12 signaling control susceptibility to contact hypersensitivityStefan F Martin
Allergy Research Group, Department of Dermatology, University Medical Center Freiburg, D 79104 Freiburg, Germany
J Exp Med 205:2151-62. 2008..Finally, CHS was inducible in germ-free wild-type and IL-12Rbeta2-deficient mice, but not in germ-free TLR4/IL-12Rbeta2 double deficient mice, suggesting that the necessary TLR activation may proceed via endogenous ligands...
- An absolute requirement for STAT4 and a role for IFN-gamma as an amplifying factor in IL-12 induction of the functional IL-18 receptor complexM Nakahira
Department of Oncology, Biomedical Research Center, Osaka University Graduate School of Medicine, 2 2 Yamada oka, Suita, Osaka 565 0871, Japan
J Immunol 167:1306-12. 2001..IL-12 induction of an IL-18R complex and IL-18Rbeta mRNA expression was not observed in STAT4-deficient (STAT4(-/-)) T cells and was substantially decreased in IFN-gamma(-/-) T cells...
- CD4+ T-cell-mediated anti-tumor immunity can be uncoupled from autoimmunity via the STAT4/STAT6 signaling axisSheng Zhang
Department of Pathology and Molecular Medicine, McMaster University, Ontario, Canada
Eur J Immunol 39:1252-9. 2009..demonstrated that CD4(+) T-cell-mediated anti-tumor immunity and autoimmunity could be separated by modulating the STAT4/STAT6 signaling axis...
- IL-23 drives pathogenic IL-17-producing CD8+ T cellsBogoljub Ciric
Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USA
J Immunol 182:5296-305. 2009..Both STAT1 and STAT4 are required for optimal development of Tc17 cells and maximal secretion of cytokines...
- Type I IFN controls chikungunya virus via its action on nonhematopoietic cellsClementine Schilte
Department of Immunology, Unité Immunobiologie des Cellules Dendritiques, Institut Pasteur, 75724 Paris, Cedex 15, France
J Exp Med 207:429-42. 2010..This study defines an essential role for type I IFN, produced via cooperation between multiple host sensors and acting directly on nonhematopoietic cells, in the control of CHIKV...
- Epigenetic instability of cytokine and transcription factor gene loci underlies plasticity of the T helper 17 cell lineageRyuta Mukasa
Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Immunity 32:616-27. 2010..but were rapidly reversed downstream of IL-12-induced silencing of the Rorc gene by the transcription factors STAT4 and T-bet...
- Vaccine-induced protection against 3 systemic mycoses endemic to North America requires Th17 cells in miceMarcel Wuthrich
Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53706, USA
J Clin Invest 121:554-68. 2011..These data suggest that human vaccines against systemic fungal infections should be designed to induce Th17 cells if they are to be effective...
- Stat4 is critical for the balance between Th17 cells and regulatory T cells in colitisJiangnan Xu
Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD 21201, USA
J Immunol 186:6597-606. 2011..In this study, by adding Stat4 deficiency to Stat6/T-bet double knockout, we further dissected the role of Stat4 in Th1 development and colitis ..
- T helper-cell phenotype regulates atherosclerosis in mice under conditions of mild hypercholesterolemiaS A Huber
Department of Pathology, University of Vermont, Burlington, USA
Circulation 103:2610-6. 2001..T cells are implicated in atherosclerosis, but little is known about the genetic control or molecular pathways, especially under conditions of mild hypercholesterolemia...
- Th1 and Th2 mediate acute graft-versus-host disease, each with distinct end-organ targetsB Nikolic
Bone Marrow Transplantation Section, Transplantation Biology Research Center, Surgical Service, Massachusetts General Hospital Harvard Medical School, Boston, Massachusetts 02129, USA
J Clin Invest 105:1289-98. 2000b>STAT4 and STAT6 are transcription factors that play crucial roles in responding to IL-12 and IL-4, respectively. STAT4 gene knockout (STAT4(-/-)) mice have markedly reduced Th1 responses and enhanced Th2 responses...
- Regulatory functions of CD8+CD28- T cells in an autoimmune disease modelNader Najafian
Brigham and Women s Hospital, Boston, Massachusetts, USA
J Clin Invest 112:1037-48. 2003..These are the first data establishing that regulatory CD8+CD28- T cells occur in normal mice and play a critical role in disease resistance in CD28-/- animals...
- Inhibition of hormone and cytokine-stimulated osteoclastogenesis and bone resorption by interleukin-4 and interleukin-13 is associated with increased osteoprotegerin and decreased RANKL and RANK in a STAT6-dependent pathwayPy Palmqvist
Departments of Oral Cell Biology and Periodontics, Umea University, Umeå S 901 87, Sweden
J Biol Chem 281:2414-29. 2006..The data indicate that IL-4 and IL-13, via a STAT6-dependent pathway, inhibit osteoclast differentiation and bone resorption by activating receptors on osteoblasts and osteoclasts that affect the RANKL/RANK/OPG system...
- A role for IL-27 in early regulation of Th1 differentiationToshiyuki Owaki
Intractable Immune System Disease Research Center, Tokyo Medical University, Japan
J Immunol 175:2191-200. 2005..of IL-27 to induce Th1 differentiation was most prominent under Th1-polarizing conditions, but without IL-12 in a STAT4- and IFN-gamma-independent manner, and was overruled by IL-12 dose dependently...
- Effect of targeted disruption of signal transducer and activator of transcription (Stat)4 and Stat6 genes on the autoimmune diabetes development induced by multiple low doses of streptozotocinMarina Cetkovic-Cvrlje
Department of Immunology, Parker Hughes Institute, 2720 Patton Road, St Paul, MN 55113, USA
Clin Immunol 114:299-306. 2005The MLDS (multiple low doses of streptozotocin) model of diabetes was induced in Stat4(-/-), Stat6(-/-), and double-deficient Stat4(-/-)/6(-/-) mice to examine the role of STAT4/STAT6 deficiency in development of autoimmune diabetes...
- Different competitive capacities of Stat4- and Stat6-deficient CD4+ T cells during lymphophenia-driven proliferationVanesa Sanchez-Guajardo
Lymphocyte Population Biology Unit, Institute Pasteur, France
J Immunol 174:1178-87. 2005..Because Stat4 and Stat6 proteins are implicated in the Th1 vs Th2 generation and maintenance, respectively, we compare in this ..
- Synergistic effect of IL-2, IL-12, and IL-18 on thymocyte apoptosis and Th1/Th2 cytokine expressionMaria Cecilia Rodriguez-Galan
Laboratory of Experimental Immunology, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA
J Immunol 174:2796-804. 2005..The IL-2-plus-IL-18 or IL-12-plus-IL-18 effect on IFN-gamma and IL-13 expression is dependent on Stat4 and NF-kappaB but independent of Stat6, T-bet, or NFAT...
- GADD45beta/GADD45gamma and MEKK4 comprise a genetic pathway mediating STAT4-independent IFNgamma production in T cellsHongbo Chi
Section of Immunobiology, Yale University School of Medicine, New Haven, CT, USA
EMBO J 23:1576-86. 2004..During Th1 differentiation, the GADD45beta/GADD45gamma/MEKK4 pathway appears to integrate upstream signals transduced by both T cell receptor and IL12/STAT4, leading to augmented IFNgamma production in a process independent of STAT4.
- Beta-glycoglycosphingolipid-induced alterations of the STAT signaling pathways are dependent on CD1d and the lipid raft protein flotillin-2Gadi Lalazar
Liver Unit, Department of Medicine, Hebrew University Hadassah Medical Center, P O B 12000, Jerusalem, Israel, IL 91120
Am J Pathol 174:1390-9. 2009..Our results show that beta-glycosphingolipids have beneficial effects in natural killer T cell-dependent immune-mediated metabolic and malignant animal models in vivo...
- Differential requirement of signal transducer and activator of transcription-4 (Stat4) and Stat6 in a thyrotropin receptor-289-adenovirus-induced model of Graves' hyperthyroidismKimberly J Land
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Evansville, Indiana 47712, USA
Endocrinology 147:111-9. 2006..previous studies using HEK-293 cells expressing the extracellular domain of the TSH receptor (TSHR) showed that Stat4-/- mice, which lack Th1 cells, are susceptible, whereas Stat6-/- mice, which lack Th2 cells, are resistant to the ..
- Role of interleukin-12 and stat-4 in the regulation of airway inflammation and hyperreactivity in respiratory syncytial virus infectionK K Tekkanat
Department of Pediatrics, University of Michigan Medical School, 1301 Catherine, Ann Arbor, MI 48109 0602, USA
Am J Pathol 159:631-8. 2001..These studies support the importance of IL-12 in the immune response to RSV infection resulting in resolution of disease and protection from inappropriate inflammatory responses...
- Cutting edge: differential requirements for Stat4 in expression of glycosyltransferases responsible for selectin ligand formation in Th1 cellsS J White
Department of Microbiology Immunology, Northwestern University Medical School, Chicago, IL 60611, USA
J Immunol 167:628-31. 2001A role for Stat4 in IL-12-induced up-regulation of selectin ligands on Th1 cells was explored...
- Mycobacterial trehalose 6,6'-dimycolate preferentially induces type 1 helper T cell responses through signal transducer and activator of transcription 4 proteinRyuta Oiso
Department of Host Defense, Osaka City University Graduate School of Medicine, Abeno Ku, Osaka 545 8585, Japan
Microb Pathog 39:35-43. 2005..we have analyzed footpad reaction, histopathology and cytokine profile of experimental granulomatous lesions using STAT4-deficient mice...
- SLIM is a nuclear ubiquitin E3 ligase that negatively regulates STAT signalingTakashi Tanaka
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA
Immunity 22:729-36. 2005..Here, we report on a nuclear protein that contains both PDZ and LIM domains and that interacts with activated STAT4 molecules...
- Early target genes of IL-12 and STAT4 signaling in th cellsRiikka J Lund
Turku Centre for Biotechnology, Turku University and Abo Akademi, Turku Graduate School of Biomedical Sciences, Turku University, Turku, Finland
J Immunol 172:6775-82. 2004IL-12 signaling through STAT4 is essential for induction of optimal levels of IFN-gamma production and commitment of Th1 cells...
- Frontline: absence of functional STAT4 activation despite detectable tyrosine phosphorylation induced by murine IFN-alphaLisa S Berenson
Department of Pathology and Center for Immunology, Washington University School of Medicine, St Louis, MO 63110, USA
Eur J Immunol 34:2365-74. 2004We previously reported that IL-12, but not IFN-alphaA/D, induces T helper type (Th) 1 development and STAT4 phosphorylation in murine CD4+ T cells...
- STAT4 is required for antibacterial defense but enhances mortality during polymicrobial sepsisC J Godshall
Veterans Affairs Medical Center and Department of Surgery, University of Louisville School of Medicine, Louisville, Kentucky 40292, USA
Clin Diagn Lab Immunol 8:1044-8. 2001The signal transducer and activator of transcription factor 4 (STAT4) pathway mediates the intracellular effects of interleukin-12 (IL-12), leading to the production of gamma interferon, induction of a T helper type 1 response, and ..
- Cytokines, Jaks, Stats, health and diseaseM P Brown
Cell and Gene Therapy Program, St Jude Children s Research Hospital, Memphis, Tennessee, USA
Aust N Z J Med 29:73-8. 1999
- STATs as activators of apoptosisC Schindler
Dept of Microbiology, Columbia University, NY 10032, USA
Trends Cell Biol 8:97-8. 1998..However, STATs appear to have a dark side as well and contribute to programmed cell death. Intriguingly, a recent study suggests that this might occur in a manner that is distinct from the standard STAT signalling paradigm...
- A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17Heon Park
Department of Immunology, University of Washington, Seattle, Washington 98195, USA
Nat Immunol 6:1133-41. 2005..Thus, IL-17 expression characterizes a unique T helper lineage that regulates tissue inflammation...
- Effect of targeted disruption of STAT4 and STAT6 on the induction of experimental autoimmune encephalomyelitisT Chitnis
Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
J Clin Invest 108:739-47. 2001..Here we used animals with targeted deletion of the STAT4 or STAT6 genes to determine the role of these signaling molecules in EAE...
- Genome-wide isolation of growth and obesity QTL using mouse speed congenic strainsCharles R Farber
Department of Animal Science, University of California Davis, One Shields Ave, Davis, CA 95016 8521, USA
BMC Genomics 7:102. 2006..To confirm and further characterize each QTL, two panels of speed congenic strains were developed by introgressing CAST/EiJ (CAST) QTL alleles onto either mutant C57Bl/6J-hg/hg (HG) or wild type C57Bl/6J (B6) genetic backgrounds...
- STAT4 is required for interleukin-12-induced chromatin remodeling of the CD25 locusAudrey O'Sullivan
Department of Microbiology and Immunology and the Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
J Biol Chem 279:7339-45. 2004Signal transducer and activator of transcription 4 (STAT4) is a critical mediator of interleukin-12 (IL-12)-stimulated inflammatory immune responses...
- Allograft rejection requires STAT5a/b-regulated antiapoptotic activity in T cells but not B cellsYe Zhang
Division of Immunology and Organ Transplantation, Department of Surgery, University of Texas Medical School, Houston, TX 77030, USA
J Immunol 176:128-37. 2006..Thus, activated STAT5a/b-/- T cells produce cytokines prior to entering apoptosis, thereby promoting differentiation of B cells yielding donor-specific IgM and IgG Ab that mediate allograft rejection...
- Contrasting roles for STAT4 and STAT6 signal transduction pathways in murine renal ischemia-reperfusion injuryNaoko Yokota
Division of Nephrology, Johns Hopkins Univ School of Medicine, Rm 970, 720 Rutland Ave, Baltimore, MD 21205, USA
Am J Physiol Renal Physiol 285:F319-25. 2003..We therefore hypothesized that mice that were STAT4 deficient would be protected from renal IRI and that STAT6-deficient mice would have a more severe course...
- Differential contribution of IL-4 and STAT6 vs STAT4 to the development of lupus nephritisRam Raj Singh
University of Cincinnati College of Medicine, Department of Internal Medicine, Veterans Affairs Medical Center and Children s Medical Center, Cincinnati, OH 45220, USA
J Immunol 170:4818-25. 2003..b>STAT4 deficiency, however, decreases type 1 and increases type 2 cytokine responses, and accelerates nephritis, in the ..
- CD4+ T cells mediate abscess formation in intra-abdominal sepsis by an IL-17-dependent mechanismDoo Ryeon Chung
Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
J Immunol 170:1958-63. 2003..induction of abscesses required T cell costimulation via the CD28-B7 pathway, and T cell transfer experiments with STAT4(-/-) and STAT6(-/-) mice demonstrated that this host response is dependent on STAT4 signaling...
- Adenovirus-mediated interferon gamma gene therapy for allergic asthma: involvement of interleukin 12 and STAT4 signalingAruna K Behera
Division of Allergy and Immunology, Joy McCann Culverhouse Airway Disease Center, University of South Florida College of Medicine, Tampa, FL 33620, USA
Hum Gene Ther 13:1697-709. 2002..The IFN-gamma effects were dependent on IL-12 and STAT4 (signal transducer and activator of transcription 4), as mice treated with antibodies to IL-12 and STAT4 deficient ..
- Physiological mechanisms of regulating alloimmunity: cytokines, CTLA-4, CD25+ cells, and the alloreactive T cell clone sizeMasayuki Sho
Department of Medicine, Children s Hospital, Laboratory of Immunogenetics and Transplantation, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
J Immunol 169:3744-51. 2002..D2 (minor mismatch) and C57BL/6 (major mismatch), into BALB/c recipients. Recipients were wild type, STAT4(-/-) (Th1 deficient), or STAT6(-/-) (Th2 deficient) mice...
- IL-12 signaling drives CD8+ T cell IFN-gamma production and differentiation of KLRG1+ effector subpopulations during Toxoplasma gondii InfectionDouglas C Wilson
Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912, USA
J Immunol 180:5935-45. 2008..gondii...
- Stat4-null non-obese diabetic mice: protection from diabetes and experimental allergic encephalomyelitis, but with concomitant epitope spreadRosemary J Boyton
Department of Infectious Diseases and Transplantation Biology Group, Medical Research Council, Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK
Int Immunol 17:1157-65. 2005..for molecules involved in cytokine receptor signal transduction, signal transducer and activator of transcription (Stat4) and Stat6...
- Deletion of MyD88 markedly attenuates sepsis-induced T and B lymphocyte apoptosis but worsens survivalOctavia M Peck-Palmer
Department of Anesthesiology, Division of Laboratory and Genomic Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
J Leukoc Biol 83:1009-18. 2008..TLR4, and IL-1R), intracellular signaling proteins (MyD88 and TRIF), cytoplasmic transcription factors (STAT1 and STAT4), and the MAPK pathway (JNK1) in sepsis-induced lymphocyte apoptosis...
- Autoimmune diabetes is blocked in Stat4-deficient miceZandong Yang
Department of Internal Medicine, Division of Endocrinology and Metabolism, University of Virginia, P O Box 801413, Charlottesville, VA 22908, USA
J Autoimmun 22:191-200. 2004..b>STAT4 mediates IL-12 signaling and regulates T helper 1 (Th1) cell differentiation...
- Stat4 suppresses the proliferation of connective tissue-type mast cellsTatsuki R Kataoka
Department of Pathology, Medical School Graduate School of Frontier Bioscience, Osaka University, Osaka, Japan
Lab Invest 88:856-64. 2008..b>Stat4 is also expressed in T cells and plays important roles in their homeostasis...
- Signal transducer and activator of transcription 4 (STAT4), but not IL-12 contributes to Pseudomonas aeruginosa-induced lung inflammation in miceRory O'Sullivan
Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada B3K 6R8
Immunobiology 213:469-79. 2008..through its associated intracellular signaling molecule, the signal transducer and activator of transcription 4 (STAT4). To examine a specific role of IL-12 and STAT4 in P...
- Structure of the amino-terminal protein interaction domain of STAT-4U Vinkemeier
Laboratory of Molecular Cell Biology and Laboratories of Molecular Biophysics, The Rockefeller University, New York, NY 10021, USA
Science 279:1048-52. 1998..Mutagenesis of an invariant tryptophan residue at the heart of this interface abolished cooperative DNA binding by the full-length protein in vitro and reduced the transcriptional response after cytokine stimulation in vivo...
- PHI-381: A Novel Anti-Leukemic AgentMarina Cetkovic Cvrlje; Fiscal Year: 2003..The knowledge gained from these studies described under Specific Aims 1-2 is expected to facilitate the design of innovative treatment regimens employing COBRA-1 for the treatment of metastatic solid tumors. ..
- IMMUNOLOGICAL DISEASE MECHANISMSSankar Ghosh; Fiscal Year: 2006..These accomplishments more than fulfill the promises made in our initial application to establish an NlAlD training program in immunology. In the next five years we expect to consolidate and expand on these gains. ..
- IMMUNE PROMOTION OF REMYELINATIONMoses Rodriguez; Fiscal Year: 2008..Our findings are expected to provide new insights into the enhancement of remyelination in diseases such as multiple sclerosis. [unreadable] [unreadable]..
- T cell Function in Murine Model of Multiple SclerosisMoses Rodriguez; Fiscal Year: 2010..The findings are expected to provide new insights into the pathogenesis of axonal and neuronal injury in demyelinating disorders such as multiple sclerosis. ..
- Tumor-induced immune suppression.Suzanne Ostrand Rosenberg; Fiscal Year: 2010..abstract_text> ..
- CHARACTERIZATION OF A MAJOR OBESITY LOCUSCharles Farber; Fiscal Year: 2008..Lastly, aim 3 uses a genetical genomics approach to map eQTL for genes within the congenic interval. Data from these aims will enhance our understanding of the genetics and physiology of obesity. ..