JOHN J O'SHEA

Summary

Affiliation: National Institutes of Health
Country: USA

Publications

  1. pmc Lymphopenic mice reconstituted with limited repertoire T cells develop severe, multiorgan, Th2-associated inflammatory disease
    Joshua D Milner
    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 104:576-81. 2007
  2. pmc Distinct requirements for T-bet in gut innate lymphoid cells
    Giuseppe Sciumè
    Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Exp Med 209:2331-8. 2012
  3. ncbi request reprint In search of magic bullets: the golden age of immunotherapeutics
    JOHN J O'SHEA
    Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA Electronic address
    Cell 157:227-40. 2014
  4. pmc JAK Kinases in Health and Disease: An Update
    Arian Laurence
    Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Open Rheumatol J 6:232-44. 2012
  5. doi request reprint Back to the future: oral targeted therapy for RA and other autoimmune diseases
    JOHN J O'SHEA
    Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Department of Health and Human Services, Building 10, Rm 13C103C, 10 Center Drive, Bethesda, MD 20892 1930, USA
    Nat Rev Rheumatol 9:173-82. 2013
  6. pmc Janus kinase inhibitors in autoimmune diseases
    JOHN J O'SHEA
    Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892 1930, USA
    Ann Rheum Dis 72:ii111-5. 2013
  7. pmc JAK and STAT signaling molecules in immunoregulation and immune-mediated disease
    JOHN 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
  8. pmc Summit on cell therapy for cancer: The importance of the interaction of multiple disciplines to advance clinical therapy
    Cornelis J M Melief
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    J Transl Med 9:107. 2011
  9. pmc The Janus kinases (Jaks)
    Kunihiro Yamaoka
    Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Genome Biol 5:253. 2004
  10. pmc Genomic views of STAT function in CD4+ T helper cell differentiation
    JOHN 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

Detail Information

Publications153 found, 100 shown here

  1. pmc Lymphopenic mice reconstituted with limited repertoire T cells develop severe, multiorgan, Th2-associated inflammatory disease
    Joshua D Milner
    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 104:576-81. 2007
    ..Limited repertoire complexity of Tregs may lead to a failure to control induction of immunopathologic responses, and limitation in repertoire complexity of conventional cells may be responsible for the Th2 phenotype...
  2. pmc Distinct requirements for T-bet in gut innate lymphoid cells
    Giuseppe Sciumè
    Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Exp Med 209:2331-8. 2012
    ..Thus, T-bet has a general importance for ILC in the gut and plays a selective and critical role in the generation of NKp46+ ILC22...
  3. ncbi request reprint In search of magic bullets: the golden age of immunotherapeutics
    JOHN J O'SHEA
    Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA Electronic address
    Cell 157:227-40. 2014
    ..In turn, these insights can inform next-generation drug discovery and refine targeted therapies for the appropriate patient subsets. ..
  4. pmc JAK Kinases in Health and Disease: An Update
    Arian Laurence
    Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Open Rheumatol J 6:232-44. 2012
    ..This review will summarize our current knowledge on these key enzymes and their associated pharmaceutical inhibitors...
  5. doi request reprint Back to the future: oral targeted therapy for RA and other autoimmune diseases
    JOHN J O'SHEA
    Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Department of Health and Human Services, Building 10, Rm 13C103C, 10 Center Drive, Bethesda, MD 20892 1930, USA
    Nat Rev Rheumatol 9:173-82. 2013
    ..We also summarize other targets involved in signalling pathways that might offer promise for therapeutic intervention in the future...
  6. pmc Janus kinase inhibitors in autoimmune diseases
    JOHN J O'SHEA
    Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892 1930, USA
    Ann Rheum Dis 72:ii111-5. 2013
    ..It is therefore timely to consider this new category of drugs and reflect on their potential roles, present and future, in the treatment of RA and related disorders...
  7. pmc JAK and STAT signaling molecules in immunoregulation and immune-mediated disease
    JOHN 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...
  8. pmc Summit on cell therapy for cancer: The importance of the interaction of multiple disciplines to advance clinical therapy
    Cornelis J M Melief
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    J Transl Med 9:107. 2011
    ..This novel assembly will generate new ideas and new collaborations and possibly increase the rate of advancement of this field...
  9. pmc The Janus kinases (Jaks)
    Kunihiro Yamaoka
    Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Genome Biol 5:253. 2004
    ..Importantly, deficiency of Jak3 is the basis of human autosomal recessive severe combined immunodeficiency (SCID); accordingly, a selective Jak3 inhibitor has been developed, forming a new class of immunosuppressive drugs...
  10. pmc Genomic views of STAT function in CD4+ T helper cell differentiation
    JOHN 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...
  11. pmc Mechanisms underlying lineage commitment and plasticity of helper CD4+ T cells
    JOHN 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...
  12. pmc Jaks and stats as therapeutic targets
    J J O'Shea
    National Institutes of Health, Bethesda, MD 20892 1820, USA
    Ann Rheum Dis 59:i115-8. 2000
    ..The possibility that these molecules could be targeted to produce novel immunosuppressive compounds is considered in this review...
  13. pmc Cytokine signaling modules in inflammatory responses
    JOHN 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
    ....
  14. ncbi request reprint T cell heterogeneity: firmly fixed, predominantly plastic or merely malleable?
    JOHN J O'SHEA
    National Institutes of Health, Bethesda, Maryland 20852 1820, USA
    Nat Immunol 9:450-3. 2008
  15. pmc Lymphoid tissue inducer-like cells are an innate source of IL-17 and IL-22
    Hiroaki 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...
  16. pmc Generation of pathogenic T(H)17 cells in the absence of TGF-β signalling
    Kamran 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...
  17. ncbi request reprint Discrete roles for histone acetylation in human T helper 1 cell-specific gene expression
    Akio Morinobu
    Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, NIAMS, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 279:40640-6. 2004
    ....
  18. pmc Diverse targets of the transcription factor STAT3 contribute to T cell pathogenicity and homeostasis
    Lydia 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...
  19. ncbi request reprint Cytokines and their role in lymphoid development, differentiation and homeostasis
    Sigrun R Hofmann
    Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Curr Opin Allergy Clin Immunol 2:495-506. 2002
    ..In this review, we will focus on recent advances in the understanding of molecular mechanisms that regulate lymphoid development, homeostasis and tolerance...
  20. pmc Retinoic acid inhibits Th17 polarization and enhances FoxP3 expression through a Stat-3/Stat-5 independent signaling pathway
    Kevin M Elias
    Howard Hughes Medical Institute National Institutes of Health Research Scholars Program, Bethesda, MD, USA
    Blood 111:1013-20. 2008
    ....
  21. ncbi request reprint 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 signaling
    Ryuta 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...
  22. pmc Cytohesin binder and regulator (cybr) is not essential for T- and dendritic-cell activation and differentiation
    Wendy 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...
  23. pmc Opposing regulation of the locus encoding IL-17 through direct, reciprocal actions of STAT3 and STAT5
    Xiang 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...
  24. pmc Interleukin-27 priming of T cells controls IL-17 production in trans via induction of the ligand PD-L1
    Kiyoshi 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...
  25. pmc Independent roles for IL-2 and GATA-3 in stimulating naive CD4+ T cells to generate a Th2-inducing cytokine environment
    Hidehiro Yamane
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Exp Med 202:793-804. 2005
    ..A MEK inhibition rescued early GATA-3 expression and responsiveness to IL-2; these cells were now capable of producing early IL-4 and undergoing subsequent Th2 differentiation...
  26. pmc T-bet regulates Th1 responses through essential effects on GATA-3 function rather than on IFNG gene acetylation and transcription
    Takashi 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...
  27. ncbi request reprint Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation
    Arian 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...
  28. pmc Discrete roles of STAT4 and STAT6 transcription factors in tuning epigenetic modifications and transcription during T helper cell differentiation
    Lai 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...
  29. pmc TGF-β and retinoic acid induce the microRNA miR-10a, which targets Bcl-6 and constrains the plasticity of helper T cells
    Hayato 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...
  30. ncbi request reprint Positive effects of glucocorticoids on T cell function by up-regulation of IL-7 receptor alpha
    Denis Franchimont
    Lymphocyte Cell Biology Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 168:2212-8. 2002
    ..These observations provide a mechanism by which glucocorticoids may have a positive influence on T cell survival and function...
  31. pmc Early Th1 cell differentiation is marked by a Tfh cell-like transition
    Shingo 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...
  32. pmc IL-21 is produced by Th17 cells and drives IL-17 production in a STAT3-dependent manner
    Lai 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...
  33. pmc Reversal of CD8 T-cell-mediated mucocutaneous graft-versus-host-like disease by the JAK inhibitor tofacitinib
    Naoko Okiyama
    Dermatology Branch, National Cancer Institute, Bethesda, Maryland, USA
    J Invest Dermatol 134:992-1000. 2014
    ..Tofacitinib may be an effective drug for treatment against CD8 T-cell-mediated mucocutaneous diseases in patients with GVHD. ..
  34. pmc The transcription factors STAT5A/B regulate GM-CSF-mediated granulopoiesis
    Akiko 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...
  35. pmc Tissue inhibitor of metalloproteinase 1 is preferentially expressed in Th1 and Th17 T-helper cell subsets and is a direct STAT target gene
    Adewole Adamson
    Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA
    PLoS ONE 8:e59367. 2013
    ..Finally, we demonstrate that when restricted to T cells, expression of TIMP1 promotes neuropathology in experimental allergic encephalomyelitis...
  36. ncbi request reprint IFN regulatory factor-4 and -8 govern dendritic cell subset development and their functional diversity
    Tomohiko 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...
  37. pmc T-cell-expressed proprotein convertase furin is essential for maintenance of peripheral immune tolerance
    Marko 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...
  38. pmc Tpl2 kinase regulates T cell interferon-gamma production and host resistance to Toxoplasma gondii
    Wendy 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...
  39. pmc A mouse model of HIES reveals pro- and anti-inflammatory functions of STAT3
    Scott M Steward-Tharp
    Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD
    Blood 123:2978-87. 2014
    ..We found that these mice were susceptible to bacterial infection that was partially corrected by HSCT using wild-type bone marrow, emphasizing the role played by the epithelium in the pathophysiology of HIES. ..
  40. pmc Lyn kinase controls basophil GATA-3 transcription factor expression and induction of Th2 cell differentiation
    Nicolas 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...
  41. pmc The gene encoding the hematopoietic stem cell regulator CCN3/NOV is under direct cytokine control through the transcription factors STAT5A/B
    Akiko 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...
  42. ncbi request reprint A distal region in the interferon-gamma gene is a site of epigenetic remodeling and transcriptional regulation by interleukin-2
    Jay 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...
  43. ncbi request reprint CXCL12 signaling is independent of Jak2 and Jak3
    Masato 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...
  44. pmc CD4+ FoxP3+ regulatory T cells confer infectious tolerance in a TGF-beta-dependent manner
    John 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...
  45. pmc Helper T-cell differentiation and plasticity: insights from epigenetics
    Kiyoshi 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...
  46. pmc New complexities in helper T cell fate determination and the implications for autoimmune diseases
    Hiroaki 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...
  47. pmc BACH2 represses effector programs to stabilize T(reg)-mediated immune homeostasis
    Rahul Roychoudhuri
    Center for Cancer Research, National Cancer Institute, National Institutes of Health NIH, Bethesda, Maryland 20892, USA
    Nature 498:506-10. 2013
    ..These findings identify BACH2 as a key regulator of CD4(+) T-cell differentiation that prevents inflammatory disease by controlling the balance between tolerance and immunity. ..
  48. ncbi request reprint Signaling by IL-12 and IL-23 and the immunoregulatory roles of STAT4
    Wendy T Watford
    Molecular Immunology and Inflammation Branch, NIAMS, National Institutes of Health, Bethesda, MD 20892 1820, USA
    Immunol Rev 202:139-56. 2004
    ..In contrast, IL-23 promotes end-stage inflammation. Targeting IL-12, IL-23, and their downstream signaling elements would therefore be logical strategies for the treatment of immune-mediated diseases...
  49. ncbi request reprint 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
  50. pmc Stat5a/b are essential for normal lymphoid development and differentiation
    Zhengju 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...
  51. ncbi request reprint Characterization and analysis of the proximal Janus kinase 3 promoter
    Martin 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...
  52. pmc STAT4 serine phosphorylation is critical for IL-12-induced IFN-gamma production but not for cell proliferation
    Akio 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...
  53. pmc STATs shape the active enhancer landscape of T cell populations
    Golnaz 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...
  54. pmc T helper 17 cell heterogeneity and pathogenicity in autoimmune disease
    Kamran 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...
  55. pmc Tumor progression locus 2 (Map3k8) is critical for host defense against Listeria monocytogenes and IL-1 beta production
    Lisa 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...
  56. pmc Proprotein convertase furin is preferentially expressed in T helper 1 cells and regulates interferon gamma
    Marko 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...
  57. pmc Global mapping of H3K4me3 and H3K27me3 reveals specificity and plasticity in lineage fate determination of differentiating CD4+ T cells
    Gang 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...
  58. ncbi request reprint Probabilistic regulation of IL-4 production in Th2 cells: accessibility at the Il4 locus
    Liying Guo
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Immunity 20:193-203. 2004
    ..Induction of VA accessibility is sensitive to cycloheximide, suggesting an additional factor(s) is needed. Thus, opening of VA is a probabilistic event determining which Th2 cells transcribe Il4...
  59. pmc Selective regulatory function of Socs3 in the formation of IL-17-secreting T cells
    Zhi 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...
  60. pmc Type I IFN induces binding of STAT1 to Bcl6: divergent roles of STAT family transcription factors in the T follicular helper cell genetic program
    Shingo Nakayamada
    Lymphocyte Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892
    J Immunol 192:2156-66. 2014
    ..These data suggest that type I IFNs (IFN-α/β) and STAT1 can contribute to some features of TFH cells but are inadequate in inducing complete programming of this subset. ..
  61. pmc 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...
  62. pmc Jak3 negatively regulates dendritic-cell cytokine production and survival
    Kunihiro 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...
  63. ncbi request reprint Jak3 and the pathogenesis of severe combined immunodeficiency
    JOHN J O'SHEA
    Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, MSC 1820, 10 Center Drive, Bethesda, MD 20892, USA
    Mol Immunol 41:727-37. 2004
    ..Further study of Jak3 will hopefully provide insights into the clinical treatment of patients suffering from immune-mediated diseases...
  64. ncbi request reprint Cytokines and transcription factors that regulate T helper cell differentiation: new players and new insights
    Davide Agnello
    Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Building 10, Room 9N262, 10 Center Drive, MSC 1820, Bethesda, Maryland 20802 1820, USA
    J Clin Immunol 23:147-61. 2003
    ..The transcription factors Stat6, GATA-3, c-Maf, NFATs, and the cytokine IL-4 promote TH2 differentiation. These key regulators of TH differentiation are the subject of this review...
  65. pmc Helper T-cell identity and evolution of differential transcriptomes and epigenomes
    Golnaz Vahedi
    Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institutes of Arthritis, Musculoskeletal and Skin Diseases, Bethesda, MD, USA
    Immunol Rev 252:24-40. 2013
    ....
  66. pmc The role of IL-15 in activating STAT5 and fine-tuning IL-17A production in CD4 T lymphocytes
    Pushpa Pandiyan
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 189:4237-46. 2012
    ..Taken together, these data indicate that IL-15 has a negative regulatory role in fine-tuning of IL-17A production and Th17-mediated inflammation...
  67. pmc Jakinibs: a new class of kinase inhibitors in cancer and autoimmune disease
    Apostolos 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...
  68. pmc Transcriptional and epigenetic control of T helper cell specification: molecular mechanisms underlying commitment and plasticity
    Yuka 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...
  69. pmc Nonredundant roles for Stat5a/b in directly regulating Foxp3
    Zhengju 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...
  70. pmc New insights into T cell biology and T cell-directed therapy for autoimmunity, inflammation, and immunosuppression
    Scott 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...
  71. pmc The Current STATus of lymphocyte signaling: new roles for old players
    Adewole 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...
  72. pmc Signal transduction pathways and transcriptional regulation in Th17 cell differentiation
    Kiyoshi 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...
  73. pmc Elevating calcium in Th2 cells activates multiple pathways to induce IL-4 transcription and mRNA stabilization
    Liying Guo
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 181:3984-93. 2008
    ..p38 also regulates IL-4 production by mRNA stabilization. TCR stimulation also phosphorylates p38, partially through the calcium-dependent pathway; activated p38 is required for optimal IL-4 and IFN-gamma...
  74. pmc Distinct functions for the transcription factors GATA-3 and ThPOK during intrathymic differentiation of CD4(+) T cells
    Lie Wang
    Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA
    Nat Immunol 9:1122-30. 2008
    ..We propose that GATA-3 acts as a specification factor for the CD4(+) lineage 'upstream' of the ThPOK-controlled CD4(+) commitment checkpoint...
  75. pmc In TH2 cells the Il4 gene has a series of accessibility states associated with distinctive probabilities of IL-4 production
    Liying Guo
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, and Cancer Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 99:10623-8. 2002
    ..This finding suggests a regulation of IL-4 expression keyed to the function of this cytokine in cell/cell interactions and in the regulation of threshold responses...
  76. ncbi request reprint Spontaneous and homeostatic proliferation of CD4 T cells are regulated by different mechanisms
    Booki Min
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 174:6039-44. 2005
    ..Our results reveal the complexity and heterogeneity of lymphopenia-driven T cell proliferation and suggest that they may have fundamentally distinct roles in the maintenance of CD4 T cell homeostasis...
  77. pmc Basophils produce IL-4 and accumulate in tissues after infection with a Th2-inducing parasite
    Booki Min
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Dr, Bldg 10, Bethesda, MD 20892, USA
    J Exp Med 200:507-17. 2004
    ..Thus, infection with a parasite that induces a "Th2-type response" resulted in accumulation of tissue basophils, and these cells, stimulated by a non-FcR cross-linking mechanism, are a principal source of in vivo IL-4 production...
  78. ncbi request reprint A new modality for immunosuppression: targeting the JAK/STAT pathway
    JOHN 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 Drug Discov 3:555-64. 2004
  79. pmc Helper T cell diversity and plasticity
    Shingo 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...
  80. ncbi request reprint Cytokines and autoimmunity
    JOHN 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...
  81. pmc Signal transduction and Th17 cell differentiation
    JOHN 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...
  82. pmc The transcription factor GATA3 actively represses RUNX3 protein-regulated production of interferon-gamma
    Ryoji Yagi
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Immunity 32:507-17. 2010
    ..Thus, the Runx3-mediated pathway, actively suppressed by GATA3, induces IFN-gamma production in a STAT4- and T-bet-independent manner...
  83. pmc STAT3 transcription factor promotes instability of nTreg cells and limits generation of iTreg cells during acute murine graft-versus-host disease
    Arian 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
    ....
  84. doi request reprint Th17 cells: a new fate for differentiating helper T cells
    Zhi 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...
  85. pmc 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...
  86. pmc Distinct regulation of interleukin-17 in human T helper lymphocytes
    Zhi 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...
  87. pmc Functional and epigenetic studies reveal multistep differentiation and plasticity of in vitro-generated and in vivo-derived follicular T helper cells
    Kristina 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...
  88. pmc New insights into the roles of Stat5a/b and Stat3 in T cell development and differentiation
    Lai 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...
  89. ncbi request reprint Regulation of IL-17 production in human lymphocytes
    Zhi 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...
  90. ncbi request reprint Neonates support lymphopenia-induced proliferation
    Booki Min
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Immunity 18:131-40. 2003
    ..CD44(bright) CD4 T cells in neonates have a wide repertoire as judged by the distribution of Vbeta expression. Thus, lymphopenia-induced T cell proliferation is a physiologic process that occurs during the early postnatal period...
  91. pmc Interleukin 2 plays a central role in Th2 differentiation
    Javier Cote-Sierra
    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 101:3880-5. 2004
    ..Thus, IL-2 plays a critical role in the polarization of naive CD4 T cells to the Th2 phenotype...
  92. ncbi request reprint New strategies for immunosuppression: interfering with cytokines by targeting the Jak/Stat pathway
    JOHN 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...
  93. pmc Inflammasome-mediated disease animal models reveal roles for innate but not adaptive immunity
    Susannah 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...
  94. ncbi request reprint IFN-gamma mediates the death of Th1 cells in a paracrine manner
    Kathryn 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...
  95. ncbi request reprint Cytokine signaling in 2002: new surprises in the Jak/Stat pathway
    JOHN 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...
  96. pmc Antigen challenge leads to in vivo activation and elimination of highly polarized TH1 memory T cells
    Nobuki Hayashi
    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 99:6187-91. 2002
    ..Thus, antigenic challenge of mice possessing resting memory TH1 CD4 T cells leads to the unanticipated loss of most of the specific cells and an apparent depletion rather than enhancement of immunologic memory...
  97. pmc Transforming growth factor-beta production and myeloid cells are an effector mechanism through which CD1d-restricted T cells block cytotoxic T lymphocyte-mediated tumor immunosurveillance: abrogation prevents tumor recurrence
    Masaki Terabe
    Molecular Immunogenetics and Vaccine Research Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Exp Med 198:1741-52. 2003
    ....
  98. pmc Therapeutic targeting of Janus kinases
    Marko 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...
  99. pmc Jak3-independent trafficking of the common gamma chain receptor subunit: chaperone function of Jaks revisited
    Sigrun 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...
  100. pmc STAT5 isoforms: controversies and clarifications
    Haydee 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...