Research Topics
Genomes and Genes
| JOHN J O'SHEASummaryAffiliation: National Institutes of Health Country: USA Publications
| Collaborators
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Detail Information
Publications
New directions in cellular therapy of cancer: a summary of the summit on cellular therapy for cancerDavid F Stroncek
Department of Transfusion Medicine, Clinical Center, NIH, Bethesda, USA
J Transl Med 10:48. 2012..In the future, combinations of adoptive transfer of T cells and specific vaccination against the cognate antigen can be envisaged to further enhance the effectiveness of these therapies...
New strategies for immunosuppression: interfering with cytokines by targeting the Jak/Stat pathwayJOHN J O'SHEA
Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892 1820, USA
Curr Opin Rheumatol 17:305-11. 2005..This review will discuss strategies to develop novel immunosuppressants that arise from advances in the understanding of cytokine signaling...- A new modality for immunosuppression: targeting the JAK/STAT pathwayMarko Pesu
Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
Nat Rev Drug Discov 3:555-64. 2004 - Cytokine signaling in 2002: new surprises in the Jak/Stat pathwayJOHN J O'SHEA
Molecular Immunology and Inflammation Branch, National Institutes of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20852, USA
Cell 109:S121-31. 2002..This review focuses on recent advances in the field and highlights some of the most active areas of Jak-Stat pathway research... - Cytokines and autoimmunityJOHN J O'SHEA
Lymphocyte Cell Biology Section, Arthritis and Rheumatism Branch and Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
Nat Rev Immunol 2:37-45. 2002..The balance between the pro-inflammatory and immunosuppressive functions of these well-known cytokines and the implications for the pathogenesis of autoimmune disease is the focus of this review... - Lymphoid tissue inducer-like cells are an innate source of IL-17 and IL-22Hiroaki Takatori
Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20892, USA
J Exp Med 206:35-41. 2009..Thus, it appears that splenic LTi-like cells are a rapid source of IL-17 and IL-22, which might contribute to dynamic organization of secondary lymphoid organ structure or host defense... - Generation of pathogenic T(H)17 cells in the absence of TGF-β signallingKamran Ghoreschi
Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
Nature 467:967-71. 2010..These data indicate an alternative mode for T(H)17 differentiation. Consistent with genetic data linking IL23R with autoimmunity, our findings re-emphasize the importance of IL-23 and therefore may have therapeutic implications... - Diverse targets of the transcription factor STAT3 contribute to T cell pathogenicity and homeostasisLydia Durant
Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20892, USA
Immunity 32:605-15. 2010..Thus, STAT3 orchestrates multiple critical aspects of T cell function in inflammation and homeostasis... - Retinoic acid inhibits Th17 polarization and enhances FoxP3 expression through a Stat-3/Stat-5 independent signaling pathwayKevin M Elias
Howard Hughes Medical Institute National Institutes of Health Research Scholars Program, Bethesda, MD, USA
Blood 111:1013-20. 2008.... 
Interleukin-27 priming of T cells controls IL-17 production in trans via induction of the ligand PD-L1Kiyoshi Hirahara
Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Immunity 36:1017-30. 2012..Thus, these data identify a suppressive activity of IL-27, by which CD4(+) T cells can restrict differentiation of Th17 cells in trans...- Activated STAT4 has an essential role in Th1 differentiation and proliferation that is independent of its role in the maintenance of IL-12R beta 2 chain expression and signalingRyuta Nishikomori
Mucosal Immunity Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases NIH, Bethesda, MD 20892, USA
J Immunol 169:4388-98. 2002..This implies that STAT4 is an essential element in the early events of Th1 differentiation... - Cytohesin binder and regulator (cybr) is not essential for T- and dendritic-cell activation and differentiationWendy T Watford
LCBS MIIB NIAMS NIH, Bldg 10, Room 9N256, MSC 1820, 10 Center Dr, Bethesda, MD 20892 1820, USA
Mol Cell Biol 26:6623-32. 2006..Previous in vitro studies using overexpression or short interfering RNA inhibition of the levels of Cybr protein appear to have overestimated its immunological role... - Interleukin-2 signaling via STAT5 constrains T helper 17 cell generationArian Laurence
Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Immunity 26:371-81. 2007..We conclude that in addition to the promotion of activation-induced cell death of lymphocytes and the generation of Treg cells, inhibition of Th17 polarization appears to be an important function of IL-2... - Early Th1 cell differentiation is marked by a Tfh cell-like transitionShingo Nakayamada
Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Immunity 35:919-31. 2011..Our data argue that Tfh and Th1 cells share a transitional stage through the signal mediated by STAT4, which promotes both phenotypes. However, T-bet represses Tfh cell functionalities, promoting full Th1 cell differentiation... - Opposing regulation of the locus encoding IL-17 through direct, reciprocal actions of STAT3 and STAT5Xiang Ping Yang
Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA
Nat Immunol 12:247-54. 2011..Thus, the balance rather than the absolute magnitude of these signals determined the propensity of cells to make a key inflammatory cytokine... 
T-bet regulates Th1 responses through essential effects on GATA-3 function rather than on IFNG gene acetylation and transcriptionTakashi Usui
Mucosal Immunity Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious Disease NIAID, National Institutes of Health NIH, Bethesda, MD 20892, USA
J Exp Med 203:755-66. 2006..Thus, the principal function of T-bet in developing Th1 cells is to negatively regulate GATA-3 rather than to positively regulate the IFNG gene...- TGF-β and retinoic acid induce the microRNA miR-10a, which targets Bcl-6 and constrains the plasticity of helper T cellsHayato Takahashi
Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA
Nat Immunol 13:587-95. 2012..We also found that miR-10a limited differentiation into the T(H)17 subset of helper T cells and therefore represents a factor that can fine-tune the plasticity and fate of helper T cells... - The transcription factors STAT5A/B regulate GM-CSF-mediated granulopoiesisAkiko Kimura
Laboratory of Genetics and Physiology, National Institute of Diabetes and Digestive and Kidney Diseases NIDDK, National Institutes of Health NIH, Bethesda, MD, USA
Blood 114:4721-8. 2009..Finally, transcriptome analysis indicated that STAT5A/B directs GM-CSF signaling through the regulation of proliferation and survival genes... - IL-21 is produced by Th17 cells and drives IL-17 production in a STAT3-dependent mannerLai Wei
Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
J Biol Chem 282:34605-10. 2007..These data argue that IL-21 serves as an autocrine factor secreted by Th17 cells that promotes or sustains Th17 lineage commitment... - Tpl2 kinase regulates T cell interferon-gamma production and host resistance to Toxoplasma gondiiWendy T Watford
Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
J Exp Med 205:2803-12. 2008..These data underscore the role of Tpl2 as a regulator of T helper cell lineage decisions and demonstrate that Tpl2 has an important functional role in the regulation of Th1 responses... - T-cell-expressed proprotein convertase furin is essential for maintenance of peripheral immune toleranceMarko Pesu
Molecular Immunology and Inflammation Branch, National Institute for Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
Nature 455:246-50. 2008..Targeting furin has emerged as a strategy in malignant and infectious disease. Our results suggest that inhibiting furin might activate immune responses, but may result in a breakdown in peripheral tolerance... - Discrete roles of STAT4 and STAT6 transcription factors in tuning epigenetic modifications and transcription during T helper cell differentiationLai Wei
Molecular Immunology and Inflammation Branch, NIAMS, National Institutes of Health, Bethesda MD 20892, USA
Immunity 32:840-51. 2010..Clusters of genes negatively regulated by STATs were also identified, highlighting previously unappreciated repressive roles of STATs. Therefore, STAT4 and STAT6 play wide regulatory roles in T helper cell specification... - Lyn kinase controls basophil GATA-3 transcription factor expression and induction of Th2 cell differentiationNicolas Charles
Laboratory of Immune Cell Signaling, NIAMS, National Institutes of Health, Bethesda, MD 20892, USA
Immunity 30:533-43. 2009..Our findings demonstrate that basophil-expressed Lyn kinase exerts regulatory control on Th2 cell differentiation and function... - The gene encoding the hematopoietic stem cell regulator CCN3/NOV is under direct cytokine control through the transcription factors STAT5A/BAkiko Kimura
Laboratory of Genetics and Physiology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA
J Biol Chem 285:32704-9. 2010..ChIP assays using 32D cells revealed IL-3-induced binding of STAT5A/B to a γ-interferon-activated sequences site in the Ccn3/Nov gene promoter. This is the first report that Ccn3/Nov is directly induced by cytokines through STAT5A/B... - CD4+ FoxP3+ regulatory T cells confer infectious tolerance in a TGF-beta-dependent mannerJohn Andersson
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
J Exp Med 205:1975-81. 2008..T reg cell-mediated generation of functional CD4(+)FoxP3(+) cells via this TGF-beta-dependent pathway may represent a major mechanism as to how T reg cells maintain tolerance and expand their suppressive abilities... - Stat5a/b are essential for normal lymphoid development and differentiationZhengju Yao
Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Proc Natl Acad Sci U S A 103:1000-5. 2006..Thus, deficiency of Stat5 results in severe combined immunodeficiency, similar in many respects to deficiency of IL-7R, gammac, and Jak3... - IFN regulatory factor-4 and -8 govern dendritic cell subset development and their functional diversityTomohiko Tamura
Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
J Immunol 174:2573-81. 2005..Together, IRF-4 and IRF-8 serve as a backbone of the molecular program regulating DC subset development and their functional diversity... - Helper T-cell differentiation and plasticity: insights from epigeneticsKiyoshi Hirahara
Department of Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institutes of Arthritis, and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892 1930, USA
Immunology 134:235-45. 2011..In this review, we will discuss recent progress in the understanding of how cytokines influence gene expression and epigenetic modifications, and the impact of these findings on our views of helper cell lineage commitment and plasticity... - CXCL12 signaling is independent of Jak2 and Jak3Masato Moriguchi
Molecular Immunology and Inflammation Branch, NIAMS, Laboratory of Host Defenses, NIAID, and Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
J Biol Chem 280:17408-14. 2005..Thus, we conclude that in contrast to previous reports, Jaks, especially Jak3, are unlikely to play an essential role in chemokine signaling... - New complexities in helper T cell fate determination and the implications for autoimmune diseasesHiroaki Takatori
Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Mod Rheumatol 18:533-41. 2008..Selectively targeting Tregs and Th17 cells are likely to be important strategies in the treatment of inflammatory and autoimmune diseases in humans... - A distal region in the interferon-gamma gene is a site of epigenetic remodeling and transcriptional regulation by interleukin-2Jay H Bream
Lymphocyte and Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health NIH, Bethesda, Maryland 20892 1820, USA
J Biol Chem 279:41249-57. 2004..These data led us to conclude that this distal region serves as both a target of chromatin remodeling in the IFNG locus as well as an IL-2-induced transcriptional enhancer that binds Stat5 proteins... - Cell signaling. Stat acetylation--a key facet of cytokine signaling?JOHN J O'SHEA
National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Science 307:217-8. 2005 - STATs shape the active enhancer landscape of T cell populationsGolnaz Vahedi
Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892 1930, USA
Cell 151:981-93. 2012..Thus, these findings point to a critical role of STATs as environmental sensors in dynamically molding the specialized enhancer architecture of differentiating cells... - T helper 17 cell heterogeneity and pathogenicity in autoimmune diseaseKamran Ghoreschi
Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA
Trends Immunol 32:395-401. 2011..Ideally, better understanding of expression and action of key transcription factors and the epigenetic landscape of Th17 can help explain the flexibility and diversity of interleukin-17-producing cells... - Global mapping of H3K4me3 and H3K27me3 reveals specificity and plasticity in lineage fate determination of differentiating CD4+ T cellsGang Wei
Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
Immunity 30:155-67. 2009..Our data suggest an epigenetic mechanism underlying the specificity and plasticity of effector and regulatory T cells and also provide a framework for understanding complexity of CD4(+) T helper cell differentiation... - STAT4 serine phosphorylation is critical for IL-12-induced IFN-gamma production but not for cell proliferationAkio Morinobu
Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal, and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Proc Natl Acad Sci U S A 99:12281-6. 2002..We conclude that phosphorylation of STAT4 on both tyrosine and serine residues is important in promoting normal T(H)1 differentiation and IFN-gamma secretion... - Tumor progression locus 2 (Map3k8) is critical for host defense against Listeria monocytogenes and IL-1 beta productionLisa A Mielke
Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health Bethesda, MD 20892, USA
J Immunol 183:7984-93. 2009..These studies implicate Tpl2 as an important mediator for collaboration of pattern recognition receptors with danger-associated molecular patterns to induce TNF and IL-1beta production and optimal host defense... - Characterization and analysis of the proximal Janus kinase 3 promoterMartin Aringer
Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
J Immunol 170:6057-64. 2003..Thus, transcription factors that bind these sites, especially Ets family members, are likely to be important regulators of Jak3 expression... - Proprotein convertase furin is preferentially expressed in T helper 1 cells and regulates interferon gammaMarko Pesu
MIIB NIAMS NIH, Bldg 10, Rm 9N262, 10 Center Dr, Bethesda, MD 20892, USA
Blood 108:983-5. 2006..Thus, we conclude that IL-12 induction of furin might represent a new aspect of IFN-gamma regulation and control of Th1 differentiation... - Transcriptional and epigenetic control of T helper cell specification: molecular mechanisms underlying commitment and plasticityYuka Kanno
Molecular Immunology and Inflammation Branch, National Institutes of Arthritis, and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
Annu Rev Immunol 30:707-31. 2012..In this review, recent advances in understanding T helper lineage specification and deciphering the action of transcription factors are summarized with emphasis on comprehensive views of the dynamic T cell epigenome... - Jak3 negatively regulates dendritic-cell cytokine production and survivalKunihiro Yamaoka
Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Disease, National Institutes of Health, Bldg 10, 9N256, 10 Center Dr, Bethesda, MD 20892 1820, USA
Blood 106:3227-33. 2005..These results may be relevant clinically for patients with SCID who have undergone hematopoietic stem cell transplantation and for patients who might be treated with a Jak3 inhibitor... - Signal transduction pathways and transcriptional regulation in Th17 cell differentiationKiyoshi Hirahara
Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institutes of Arthritis, and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Cytokine Growth Factor Rev 21:425-34. 2010..In this review, we will discuss the current understanding of the signaling pathways, molecular interactions, and transcriptional and epigenetic events that contribute to Th17 differentiation and acquisition of effector functions... - New insights into T cell biology and T cell-directed therapy for autoimmunity, inflammation, and immunosuppressionScott M Steward-Tharp
Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
Ann N Y Acad Sci 1183:123-48. 2010..Within this context, we examine existing T cell-directed therapies, including new agents being evaluated in clinical and preclinical studies. We also use recent findings to speculate on novel targets... - The Current STATus of lymphocyte signaling: new roles for old playersAdewole S Adamson
Molecular Immunology and Inflammation Branch, National Institutes of Arthritis, and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD 20892, USA
Curr Opin Immunol 21:161-6. 2009..Focusing on how STATs work in concert with other transcription factors will hopefully provide a better mechanistic understanding of the pathogenesis of various autoimmune diseases... - Nonredundant roles for Stat5a/b in directly regulating Foxp3Zhengju Yao
Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892 1820, USA
Blood 109:4368-75. 2007..Therefore, we conclude that Stat5a/b have an essential, nonredundant role in regulating Treg cells, and that Stat3 and Stat5a/b appear to have opposing roles in the regulation of Foxp3... - Jakinibs: a new class of kinase inhibitors in cancer and autoimmune diseaseApostolos Kontzias
Pediatric Rheumatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA
Curr Opin Pharmacol 12:464-70. 2012..Many other Jakinibs are likely to follow and in this brief review, we will discuss the state-of-the art of this new class of pharmacological agents... - Helper T cell diversity and plasticityShingo Nakayamada
Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Curr Opin Immunol 24:297-302. 2012..In this review, we highlight recent advances that pertain to this topic and the mechanisms that contribute to helper CD4(+) T cell differentiation and plasticity... - Modulation of innate and adaptive immune responses by tofacitinib (CP-690,550)Kamran Ghoreschi
Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
J Immunol 186:4234-43. 2011..Thus, CP-690,550 may improve autoimmune diseases and prevent transplant rejection by suppressing the differentiation of pathogenic Th1 and Th17 cells as well as innate immune cell signaling... - Signal transduction and Th17 cell differentiationJOHN J O'SHEA
Molecular Immunology and Inflammation Branch, National Institutes of Arthritis, and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Microbes Infect 11:599-611. 2009..Here we review our current understanding of the signaling pathways, molecular interactions and transcriptional events that lead to Th17 differentiation and effector function, as well as the epigenetic modifications that accompany them... - Genomic views of STAT function in CD4+ T helper cell differentiationJOHN J O'SHEA
Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
Nat Rev Immunol 11:239-50. 2011..Defining exactly how extrinsic signals control the specification and plasticity of T(H) cells will provide important insights and perhaps therapeutic opportunities in these diseases... - Mechanisms underlying lineage commitment and plasticity of helper CD4+ T cellsJOHN J O'SHEA
Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892 1616, USA
Science 327:1098-102. 2010..Herein, we review recent advances that pertain to this topic and the mechanisms that contribute to helper CD4+ T cell commitment and plasticity. The therapeutic implications of these new findings are also considered... - Selective regulatory function of Socs3 in the formation of IL-17-secreting T cellsZhi Chen
Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Proc Natl Acad Sci U S A 103:8137-42. 2006..We conclude that Socs3 is an essential negative regulator of IL-23 signaling, inhibition of which constrains the generation of Th17 differentiation... - STAT3 transcription factor promotes instability of nTreg cells and limits generation of iTreg cells during acute murine graft-versus-host diseaseArian Laurence
Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Immunity 37:209-22. 2012.... - Selectivity and therapeutic inhibition of kinases: to be or not to be?Kamran Ghoreschi
Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA
Nat Immunol 10:356-60. 2009..In this Perspective, we discuss the present status of Janus kinase inhibitors-a new class of immunosuppressive drugs-and the advantages and disadvantages of selectively inhibiting this class of kinase... - Regulation of IL-17 production in human lymphocytesZhi Chen
Molecular Immunology and Inflammation Branch, National Institutes of Arthritis, and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA
Cytokine 41:71-8. 2008..Targeting the production and action of this cytokine is also likely to be beneficial therapeutically for autoinflammatory and autoimmune diseases... - Distinct regulation of interleukin-17 in human T helper lymphocytesZhi Chen
National Institute of Arthritis and Musculoskeletal and Skin Diseases and National Human Genome Research Institute, NIH, Bethesda, Maryland 20892 1820, USA
Arthritis Rheum 56:2936-46. 2007..The present study was undertaken to assess the effects on naive human CD4+ T cells of cytokines known to promote murine Th17 cells... - IFN-gamma mediates the death of Th1 cells in a paracrine mannerKathryn E Foulds
Cellular Immunology Section, Human Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
J Immunol 180:842-9. 2008..Collectively, these data show the multiple mechanisms by which Th1 effector cells are efficiently eliminated in vivo... - Functional and epigenetic studies reveal multistep differentiation and plasticity of in vitro-generated and in vivo-derived follicular T helper cellsKristina T Lu
National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
Immunity 35:622-32. 2011..ChIP-Seq analyses revealed positive epigenetic markings on Tbx21, Gata3, and Rorc in Tfh-like and ex vivo Tfh cells and on Bcl6 in non-Tfh cells, supporting the concept of plasticity between Tfh and other Th cell populations... - Th17 cells: a new fate for differentiating helper T cellsZhi Chen
Molecular Immunology and Inflammation Branch, National Institutes of Arthritis, Musculoskeletal and Skin Diseases, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
Immunol Res 41:87-102. 2008..Selectively targeting the Th17 lineage may be beneficial for the treatment of inflammatory and autoimmune diseases... - The Transcription Factors Thpok and LRF Are Necessary and Partly Redundant for T Helper Cell DifferentiationAndrea C Carpenter
Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Immunity 37:622-33. 2012..These findings identify the Thpok-LRF pair as a core node of Th cell differentiation and function... - JAK and STAT signaling molecules in immunoregulation and immune-mediated diseaseJOHN J O'SHEA
Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Immunity 36:542-50. 2012..Not only have genome-wide association studies demonstrated that this pathway is highly relevant to human autoimmunity, but targeting JAKs is now a reality in immune-mediated disease... - Inflammasome-mediated disease animal models reveal roles for innate but not adaptive immunitySusannah D Brydges
Genetics and Genomics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Immunity 30:875-87. 2009..These data suggest that CAPS are true inflammasome-mediated diseases and provide insight for more common inflammatory disorders... - New insights into the roles of Stat5a/b and Stat3 in T cell development and differentiationLai Wei
Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA
Semin Cell Dev Biol 19:394-400. 2008..Therefore, Stat5a/b and Stat3 are emerging to be key players in T cell differentiation and homeostasis... - Janus kinases in immune cell signalingKamran Ghoreschi
Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Immunol Rev 228:273-87. 2009..Despite the fact that Jaks were discovered only a little more than a decade ago, at the time of writing there are 20 clinical trials underway testing the safety and efficacy of Jak inhibitors... - Therapeutic targeting of Janus kinasesMarko Pesu
Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA
Immunol Rev 223:132-42. 2008..Thus, we are learning a great deal about the feasibility and effectiveness of targeting Janus kinases, and it appears likely that this will be a fruitful strategy in a variety of settings... - Fyn kinase initiates complementary signals required for IgE-dependent mast cell degranulationValentino Parravicini
Molecular Inflammation Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892 1820, USA
Nat Immunol 3:741-8. 2002..Fyn-deficiency impaired degranulation, whereas Lyn-mediated signaling and calcium was normal. Thus, Fc epsilon RI-dependent mast cell degranulation involves cross-talk between Fyn and Lyn kinases... - Jak3-independent trafficking of the common gamma chain receptor subunit: chaperone function of Jaks revisitedSigrun R Hofmann
National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, 10 Center Dr, Bldg 10, Rm 9N256, Bethesda, MD 20892 1820, USA
Mol Cell Biol 24:5039-49. 2004..However, full-length Jak3 is required for normal trafficking of this cytokine receptor/Jak pair, a finding that has important structural and clinical implications... - STAT5 isoforms: controversies and clarificationsHaydee L Ramos
Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Biochem J 404:e1-2. 2007..This new evidence calls into question the physiological significance of this putative isoform and forces the general re-examination of proteolytically generated STAT isoforms... - Cytokine signaling modules in inflammatory responsesJOHN J O'SHEA
Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20852, USA
Immunity 28:477-87. 2008.... - De novo CIAS1 mutations, cytokine activation, and evidence for genetic heterogeneity in patients with neonatal-onset multisystem inflammatory disease (NOMID): a new member of the expanding family of pyrin-associated autoinflammatory diseasesIvona Aksentijevich
National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland 20892, USA
Arthritis Rheum 46:3340-8. 2002.... - The Yersinia effector protein YpkA induces apoptosis independently of actin depolymerizationHeiyoung Park
Molecular Immunology and Inflammation Branch, Immunoregulation Unit, National Institute and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
J Immunol 178:6426-34. 2007..A region including aa 133-262 in YpkA was sufficient for inducing apoptosis independent of localization to the plasma membrane. These data suggest that YpkA can act as a direct inducer of cell death... - Cybr, a cytokine-inducible protein that binds cytohesin-1 and regulates its activityPingtao Tang
Pulmonary Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
Proc Natl Acad Sci U S A 99:2625-9. 2002..Because the binding protein modified activation of ADP ribosylation factor by cytohesin-1, we designate this cytokine-inducible protein Cybr (cytohesin binder and regulator)... - Examining the chirality, conformation and selective kinase inhibition of 3-((3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitrile (CP-690,550)Jian Kang Jiang
NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, 9800 Medical Center Drive, Rockville, Maryland 20850, USA
J Med Chem 51:8012-8. 2008..Finally, an appraisal of the minimum energy conformation of each stereoisomer and molecular docking at Jak3 was performed in an effort to better understand each compounds selectivity and potency profiles... - Jaks and STATs: biological implicationsW J Leonard
Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892 1674, USA
Annu Rev Immunol 16:293-322. 1998..STATs then can modulate the expression of target genes. The basic biology of this system, including the range of known Jaks and STATs, is discussed, as are the defects in animals and humans lacking some of these signaling molecules... - Recent advances in understanding NF-kappaB regulationDavid L Boone
Department of Medicine, Ben May Institute for Cancer Research, IBD Research Center and Committee on Immunology, The University of Chicago, Chicago, Illinois 60637, USA
Inflamm Bowel Dis 8:201-12. 2002 - Connecting the dots from Toll-like receptors to innate immune cells and inflammatory bowel diseaseDavid L Boone
Department of Medicine, Ben May Institute for Cancer Research, The University of Chicago, Chicago, Illinois 60637, USA
J Clin Invest 111:1284-6. 2003 - The ubiquitin-modifying enzyme A20 is required for termination of Toll-like receptor responsesDavid L Boone
Department of Medicine, University of California at San Francisco, San Francisco, California 94143 0451, USA
Nat Immunol 5:1052-60. 2004..The critical function of this deubiquitinating enzyme in the restriction of TLR signals emphasizes the importance of the regulation of ubiquitin conjugation in innate immune cells... - Diverse functions of IL-2, IL-15, and IL-7 in lymphoid homeostasisAveril Ma
Department of Medicine, Biomedical Sciences Program, University of California, San Francisco, California 94143 0451, USA
Annu Rev Immunol 24:657-79. 2006..Trans-presentation also raises several novel cell biological and cellular implications concerning how cytokines support lymphoid homeostasis... - De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-kappaB signallingIngrid E Wertz
Department of Molecular Oncology, School of Medicine, University of California, Davis, Davis, California 95616, USA
Nature 430:694-9. 2004..We also provide an example of a protein containing separate ubiquitin ligase and DUB domains, both of which participate in mediating a distinct regulatory effect... - Unresolved ER Stress Inflames the IntestineAveril Ma
Department of Medicine, University of California at San Francisco, San Francisco, CA 94143 0451, USA
Cell 134:724-5. 2008..In this issue, Kaser et al. (2008) link a key mediator of endoplasmic reticulum stress, the protein XBP1, with survival of intestinal secretory epithelial cells and inflammatory bowel disease... - Encoding NF-kappaB temporal control in response to TNF: distinct roles for the negative regulators IkappaBalpha and A20Shannon L Werner
Signaling Systems Laboratory, Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, California 92093, USA
Genes Dev 22:2093-101. 2008..Our results delineate the nonredundant functions implied by the knockout phenotypes of ikappabalpha and a20, and identify the latter as a signaling cross-talk mediator controlling inflammatory and developmental responses... - DAP12 signaling directly augments proproliferative cytokine stimulation of NK cells during viral infectionsAnthony R French
Division of Pediatric Rheumatology, Department of Pediatrics, Washington University School of Medicine, St Louis, MO 63110, USA
J Immunol 177:4981-90. 2006..The impact of Ly49H-mediated signaling on NK cell proliferation is masked in the presence of high concentrations of proproliferative cytokines that nonselectively drive all NK cells to proliferate... - Interleukin-2-deficient mice develop colitis in the absence of CD28 costimulationDavid L Boone
Department of Medicine, Ben May Institute for Cancer Research, The University of Chicago, Illinois, USA
Inflamm Bowel Dis 8:35-42. 2002..This suggests that other costimulatory molecules or T-cell receptor ligation alone drive lymphocyte expansion in IL-2-deficient mice... - Homeostatic MyD88-dependent signals cause lethal inflamMation in the absence of A20Emre E Turer
Gastrointestinal Division, Department of Medicine, Biomedical Sciences Program, University of California, San Francisco, San Francisco, CA 94143, USA
J Exp Med 205:451-64. 2008..These findings provide novel insights into how physiological TLR signals are regulated... - Regulatory T cells control dendritic cell/NK cell cross-talk in lymph nodes at the steady state by inhibiting CD4+ self-reactive T cellsMagali Terme
Institut National de la Santé et de la Recherche Médicale Unité 805, Tumor Immunology and Immunotherapy, Villejuif, France
J Immunol 180:4679-86. 2008..Therefore, the DC/T cell autoreactivity leading to NK cell triggering could potentially be controlled by the coinhibition of both IL-15Ralpha and CCR5 in autoimmune disorders in which NK cells play a deleterious role... - Coordinate expression and trans presentation of interleukin (IL)-15Ralpha and IL-15 supports natural killer cell and memory CD8+ T cell homeostasisPatrick R Burkett
Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA
J Exp Med 200:825-34. 2004..These studies indicate that IL-15Ralpha defines homeostatic niches for NK and memory CD8+ T cells by controlling both the production and the presentation of IL-15 in trans to NK and CD8+ memory T cells... - Interleukin-15 and the regulation of lymphoid homeostasisJames Lodolce
Department of Medicine and the Ben May Institute for Cancer Research, University of Chicago, 5841 S. Maryland Avenue MC 6084, Chicago, IL 60637, USA
Mol Immunol 39:537-44. 2002..This review will focus on recent studies that highlight some of these functions... - The ubiquitin-editing enzyme A20 restricts nucleotide-binding oligomerization domain containing 2-triggered signalsOsamu Hitotsumatsu
UCSF Colitis Center, Gastroenterology Division, Department of Medicine, Program in Biomedical Sciences, University of California at San Francisco, San Francisco, CA 94143 0538, USA
Immunity 28:381-90. 2008..These findings indicate that A20 directly restricts NOD2 induced signals in vitro and in vivo, and provide new insights into how these signals are physiologically restricted... - Fas is not essential for lamina propria T lymphocyte homeostasisDavid L Boone
Department of Medicine, Inflammatory Bowel Disease Research Center, Committee on Immunology, The University of Chicago, IL 60637, USA
Am J Physiol Gastrointest Liver Physiol 285:G382-8. 2003..Thus our studies reveal that Fas is dispensable for LP T cell homeostasis and suggest that the intestinal inflammation observed in IL2Ralpha-/- mice is independent of defective Fas-induced cell death... - Cutting edge: murine dendritic cells require IL-15R alpha to prime NK cellsRima Koka
Department of Medicine, University of California, San Francisco, CA 94143, USA
J Immunol 173:3594-8. 2004..Finally, presentation of IL-15 by purified IL-15Ralpha/Fc in trans synergizes with IL-12 to support NK cell priming. These findings suggest that murine DCs require IL-15Ralpha to present IL-15 in trans to NK cells during NK cell priming... - Enteric flora and lymphocyte-derived cytokines determine expression of heat shock proteins in mouse colonic epithelial cellsKeishi Kojima
Department of Medicine, The MArtin Boyer Laboratory, The University of Chicago, Illinois 60637, USA
Gastroenterology 124:1395-407. 2003..Activated LPLs induce YAMC hsp expression, an effect blocked by IL-2 neutralizing antibody. CONCLUSIONS: Enteric flora and mucosal lymphocytes play a role in maintaining physiologic expression of colonocyte hsp25 and hsp72... - Generation, maintenance, and function of memory T cellsPatrick R Burkett
Department of Medicine and the Ben May Institute for Cancer Research, University of Chicago, IL 60637, USA
Adv Immunol 83:191-231. 2004 - Loss of T-bet sends host-microbe mutualism awryAveril Ma
Department of Medicine, Program in Biomedical Sciences, University of California at San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143 0451, USA
Cell 131:15-7. 2007..In this issue, Garrett et al. (2007) describe a communicable form of colitis that is induced by deficiency of the transcription factor T-bet in cells of the innate immune system... - IkappaB kinase beta phosphorylates the K63 deubiquitinase A20 to cause feedback inhibition of the NF-kappaB pathwayJessica E Hutti
Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, USA
Mol Cell Biol 27:7451-61. 2007..Phosphorylation of A20 by IKKbeta thus represents part of a novel feedback loop that regulates the duration of NF-kappaB signaling following activation of innate immune signaling pathways...