W J Leonard

Summary

Affiliation: National Institutes of Health
Country: USA

Publications

  1. pmc The molecular basis of IL-21-mediated proliferation
    Rong Zeng
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892 1674, USA
    Blood 109:4135-42. 2007
  2. ncbi request reprint IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways
    Liang Zhou
    The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, New York 10016, USA
    Nat Immunol 8:967-74. 2007
  3. ncbi request reprint Interleukin-21: basic biology and implications for cancer and autoimmunity
    Rosanne Spolski
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892 1674, USA
    Annu Rev Immunol 26:57-79. 2008
  4. pmc Priming for T helper type 2 differentiation by interleukin 2-mediated induction of interleukin 4 receptor alpha-chain expression
    Wei Liao
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Immunol 9:1288-96. 2008
  5. pmc NetPath: a public resource of curated signal transduction pathways
    Kumaran Kandasamy
    Institute of Bioinformatics, International Tech Park, Bangalore 560066, India
    Genome Biol 11:R3. 2010
  6. ncbi request reprint Cytokines and immunodeficiency diseases
    W J Leonard
    Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892 1674, USA
    Nat Rev Immunol 1:200-8. 2001
  7. ncbi request reprint Jaks and STATs: biological implications
    W 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
  8. ncbi request reprint Immune deficiencies due to defects in cytokine signaling
    John Kelly
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA
    Curr Allergy Asthma Rep 3:396-401. 2003
  9. ncbi request reprint Interleukin-21: a modulator of lymphoid proliferation, apoptosis and differentiation
    Warren J Leonard
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892 1674, USA
    Nat Rev Immunol 5:688-98. 2005
  10. pmc Interleukin-7 deficiency in rheumatoid arthritis
    Warren J Leonard
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA
    Arthritis Res Ther 7:42-3. 2005

Detail Information

Publications110 found, 100 shown here

  1. pmc The molecular basis of IL-21-mediated proliferation
    Rong Zeng
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892 1674, USA
    Blood 109:4135-42. 2007
    ..Collectively, these data indicate the involvement of the Jak-STAT, MAPK, and PI3K pathways in IL-21 signaling...
  2. ncbi request reprint IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways
    Liang Zhou
    The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, New York 10016, USA
    Nat Immunol 8:967-74. 2007
    ..IL-6 therefore orchestrates a series of 'downstream' cytokine-dependent signaling pathways that, in concert with TGF-beta, amplify RORgammat-dependent differentiation of T(H)-17 cells...
  3. ncbi request reprint Interleukin-21: basic biology and implications for cancer and autoimmunity
    Rosanne Spolski
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892 1674, USA
    Annu Rev Immunol 26:57-79. 2008
    ..The key to harnessing the power of IL-21 will depend on better understanding its range of biological actions, its mechanism of action, and the molecular basis of regulation of expression of IL-21 and its receptor...
  4. pmc Priming for T helper type 2 differentiation by interleukin 2-mediated induction of interleukin 4 receptor alpha-chain expression
    Wei Liao
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Immunol 9:1288-96. 2008
    ..Our results identify a previously unappreciated function for IL-2 in 'priming' T cells for T(H)2 differentiation and in maintaining the expression of Il4ra and other genes in T(H)2-committed cells...
  5. pmc NetPath: a public resource of curated signal transduction pathways
    Kumaran Kandasamy
    Institute of Bioinformatics, International Tech Park, Bangalore 560066, India
    Genome Biol 11:R3. 2010
    ..We anticipate NetPath to become a consolidated resource for human signaling pathways that should enable systems biology approaches...
  6. ncbi request reprint Cytokines and immunodeficiency diseases
    W J Leonard
    Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892 1674, USA
    Nat Rev Immunol 1:200-8. 2001
    ..Moreover, a comparison of the phenotypes of humans with SCID to analogous mouse-knockout models has shown not only expected similarities, but also unexpected differences in cytokine signalling between humans and mice...
  7. ncbi request reprint Jaks and STATs: biological implications
    W 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...
  8. ncbi request reprint Immune deficiencies due to defects in cytokine signaling
    John Kelly
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA
    Curr Allergy Asthma Rep 3:396-401. 2003
    ..More subtle deficiencies in cytokine signaling have also been found as causes of other forms of immunodeficiency, and the knowledge learned could lead to novel approaches to antimicrobial therapy...
  9. ncbi request reprint Interleukin-21: a modulator of lymphoid proliferation, apoptosis and differentiation
    Warren J Leonard
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892 1674, USA
    Nat Rev Immunol 5:688-98. 2005
    ..Moreover, it has antitumour activity and might have a role in the development of autoimmunity, so these findings have implications for the treatment of cancer and autoimmune diseases...
  10. pmc Interleukin-7 deficiency in rheumatoid arthritis
    Warren J Leonard
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA
    Arthritis Res Ther 7:42-3. 2005
    ....
  11. ncbi request reprint X-linked severe combined immunodeficiency: from molecular cause to gene therapy within seven years
    W J Leonard
    Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892 1674, USA
    Mol Med Today 6:403-7. 2000
    ..Furthermore, initial attempts at using gene therapy to treat patients with XSCID have been successful for more than ten months, making this disease perhaps the most promising to date for treatment with such a strategy...
  12. ncbi request reprint An indirect effect of Stat5a in IL-2-induced proliferation: a critical role for Stat5a in IL-2-mediated IL-2 receptor alpha chain induction
    H Nakajima
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Immunity 7:691-701. 1997
    ..Correspondingly, we show that Stat5a is essential for maximal responsiveness to antigenic stimuli in vivo, underscoring the physiological importance of IL-2-induced IL-2R alpha expression...
  13. ncbi request reprint JAB/SOCS1/SSI-1 is an interleukin-2-induced inhibitor of IL-2 signaling
    B Sporri
    Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
    Blood 97:221-6. 2001
    ..Thus, JAB/SOCS1/SSI-1 is an IL-2-induced inhibitor of IL-2 signaling that functions by inhibiting Jak kinase activity. This suggests an important role for JAB/SOCS1/SSI-1 in regulating T-cell responses...
  14. pmc Functional cleavage of the common cytokine receptor gamma chain (gammac) by calpain
    M Noguchi
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 94:11534-9. 1997
    ..Together, these data suggest that calpain-mediated cleavage of gammac represents a mechanism by which gammac-dependent signaling can be controlled...
  15. pmc Characterization of cDNAs encoding the murine interleukin 2 receptor (IL-2R) gamma chain: chromosomal mapping and tissue specificity of IL-2R gamma chain expression
    X Cao
    Section on Pulmonary and Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892
    Proc Natl Acad Sci U S A 90:8464-8. 1993
    ..The cloning of the murine IL-2R gamma cDNA will facilitate the investigation of the role of this protein in lymphocyte function and thymic development...
  16. pmc DNA binding site selection of dimeric and tetrameric Stat5 proteins reveals a large repertoire of divergent tetrameric Stat5a binding sites
    E Soldaini
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Maryland 20892, USA
    Mol Cell Biol 20:389-401. 2000
    ..These data provide insights into tetramer formation by Stat5a and indicate that the repertoire of potential binding sites for this transcription factor is broader than expected...
  17. ncbi request reprint The basis for IL-2-induced IL-2 receptor alpha chain gene regulation: importance of two widely separated IL-2 response elements
    H P Kim
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Immunity 15:159-72. 2001
    ..Thus, the IL-2 inducibility of the IL-2Ralpha gene is unexpectedly mediated by two widely separated regulatory Stat5-dependent elements, located both upstream and downstream of the transcription initiation sites...
  18. pmc Stat5b is essential for natural killer cell-mediated proliferation and cytolytic activity
    K Imada
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892 1674, USA
    J Exp Med 188:2067-74. 1998
    ..These data indicate an essential nonredundant role for Stat5b for potent NK cell-mediated proliferation and cytolytic activity...
  19. ncbi request reprint CIS associates with the interleukin-2 receptor beta chain and inhibits interleukin-2-dependent signaling
    M J Aman
    Laboratory of Molecular Immunology, NHLBI, National Institutes of Health, Bethesda, Maryland 20892 1674, USA
    J Biol Chem 274:30266-72. 1999
    ..On this basis, we have generated a mutant form of CIS protein with an altered SH2 domain that acts as a dominant negative and should prove useful in further understanding CIS action...
  20. ncbi request reprint HTLV-1 p12(I) protein enhances STAT5 activation and decreases the interleukin-2 requirement for proliferation of primary human peripheral blood mononuclear cells
    C Nicot
    National Cancer Institute, Basic Research Laboratory, Bethesda, MD 20892, USA
    Blood 98:823-9. 2001
    ..Blood. 2001;98:823-829)..
  21. ncbi request reprint Delineation of the regions of interleukin-2 (IL-2) receptor beta chain important for association of Jak1 and Jak3. Jak1-independent functional recruitment of Jak3 to Il-2Rbeta
    M H Zhu
    Laboratory of Molecular Immunology, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 273:10719-25. 1998
    ....
  22. ncbi request reprint Role of Bcl-2 in alpha beta T cell development in mice deficient in the common cytokine receptor gamma-chain: the requirement for Bcl-2 differs depending on the TCR/MHC affinity
    H Nakajima
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892 1674, USA
    J Immunol 162:782-90. 1999
    ....
  23. ncbi request reprint Functional association of Nmi with Stat5 and Stat1 in IL-2- and IFNgamma-mediated signaling
    M Zhu
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892 1674, USA
    Cell 96:121-30. 1999
    ....
  24. ncbi request reprint Role of Jak kinases and STATs in cytokine signal transduction
    W J Leonard
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1674, USA
    Int J Hematol 73:271-7. 2001
    ..This review summarizes salient features of the Jak-STAT pathway and focuses on the functional role of the different Jak kinases and STATs in vivo...
  25. pmc An IL-2 response element in the human IL-2 receptor alpha chain promoter is a composite element that binds Stat5, Elf-1, HMG-I(Y) and a GATA family protein
    S John
    Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, Bethesda MD, USA
    EMBO J 15:5627-35. 1996
    ..Thus, IL-2-induced IL-2R alpha promoter activity requires a complex upstream element, which appears to contain binding sites for both positive and negative regulatory factors...
  26. ncbi request reprint The role of Stat5a and Stat5b in signaling by IL-2 family cytokines
    J X Lin
    Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health, Bldg 10 Rm 7N252, 9000 Rockville Pike, Bethesda, Maryland MD 20892 1674, USA
    Oncogene 19:2566-76. 2000
    ..Oncogene (2000)...
  27. ncbi request reprint Interleukin-2 receptor gamma chain: a functional component of the interleukin-7 receptor
    M Noguchi
    Section on Pulmonary and Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892
    Science 262:1877-80. 1993
    ..These findings may help explain the defects of XSCID. Given its role in more than one cytokine receptor system, the common gamma chain (gamma c) is proposed as the designation for IL-2R gamma...
  28. ncbi request reprint Defective IL7R expression in T(-)B(+)NK(+) severe combined immunodeficiency
    A Puel
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892 1674, USA
    Nat Genet 20:394-7. 1998
    ..We now demonstrate that defective IL7R expression causes T(-)B(+)NK(+) SCID, indicating that the T-cell, but not the NK-cell, defect in XSCID results from inactivation of IL-7Ralpha signalling...
  29. pmc Different interleukin 2 receptor beta-chain tyrosines couple to at least two signaling pathways and synergistically mediate interleukin 2-induced proliferation
    M C Friedmann
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892 1674, USA
    Proc Natl Acad Sci U S A 93:2077-82. 1996
    ..In COS-7 cells, overexpression of Jak1 augmented phosphorylation of Y338 as well as Y392 and Y510, suggesting that the role for this Jak kinase may extend beyond the Jak-STAT pathway...
  30. pmc Regulation of cell-type-specific interleukin-2 receptor alpha-chain gene expression: potential role of physical interactions between Elf-1, HMG-I(Y), and NF-kappa B family proteins
    S John
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892
    Mol Cell Biol 15:1786-96. 1995
    ....
  31. pmc The role of thymic stromal lymphopoietin in CD8+ T cell homeostasis
    Yrina Rochman
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD20892 1674, USA
    J Immunol 181:7699-705. 2008
    ..Moreover, TSLP can maintain CD8(+) T cells even in the absence of IL-7. Thus, our data reveal that TSLP contributes to CD8(+) T cell homeostasis in both normal and lymphopenic conditions...
  32. ncbi request reprint The Jak-STAT pathway
    K Imada
    Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892 1674, USA
    Mol Immunol 37:1-11. 2000
    ..Moreover, the recent discovery of the CIS/SOCS/JAB/SSI family of inhibitors has contributed to understanding how this pathway is negatively regulated...
  33. pmc The same target sequences are differentially important for activation of the interleukin 2 receptor alpha-chain gene in two distinct T-cell lines
    M B Toledano
    Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892
    Proc Natl Acad Sci U S A 87:1830-4. 1990
    ..These studies provide direct evidence for a functionally significant SRE-like sequence in a gene other than c-fos and the actin genes and identify other elements that are critical for IL-2R alpha gene expression...
  34. ncbi request reprint Sp1 represses IL-2 receptor alpha chain gene expression
    D G Roman
    Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892
    New Biol 2:642-7. 1990
    ..Site-directed mutagenesis and transient transfection assays indicate that the IL2R alpha gene Sp1 serves the unusual role of repressing gene expression, most likely by competing for binding of nuclear factor(s) to the CArG box...
  35. ncbi request reprint Impaired peripheral deletion of activated T cells in mice lacking the common cytokine receptor gamma-chain: defective Fas ligand expression in gamma-chain-deficient mice
    H Nakajima
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA
    J Immunol 159:4737-44. 1997
    ..Thus, gamma c-dependent signals play a role in peripheral T cell deletion, presumably by inducing Fas ligand on activated T cells...
  36. ncbi request reprint Cloning of human Stat5B. Reconstitution of interleukin-2-induced Stat5A and Stat5B DNA binding activity in COS-7 cells
    J X Lin
    Laboratory of Molecular Immunology, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 271:10738-44. 1996
    ..The COS-7 reconstitution system described herein provides a valuable assay for further elucidation of the IL-2-activated JAK-STAT pathway...
  37. ncbi request reprint cDNA cloning and characterization of the human interleukin 13 receptor alpha chain
    M J Aman
    Laboratory of Molecular Immunology, NHLBI, National Institutes of Health, Bethesda, Maryland 20892 1674, USA
    J Biol Chem 271:29265-70. 1996
    ..Nevertheless, the overall size and length of the cytoplasmic domain of IL-13Ralpha and gammac are similar, and like gammac, IL-13Ralpha is located on chromosome X...
  38. pmc Human and simian T-cell leukemia viruses type 2 (HTLV-2 and STLV-2(pan-p)) transform T cells independently of Jak/STAT activation
    J C Mulloy
    Basic Research Laboratory, National Cancer Institute, Bethesda, Maryland 20892 4255, USA
    J Virol 72:4408-12. 1998
    ....
  39. ncbi request reprint Calcium-dependent activation of interleukin-21 gene expression in T cells
    Hyoung Pyo Kim
    Laboratory of Molecular Immunology, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 280:25291-7. 2005
    ..Thus, our studies reveal that in contrast to IL-2, a calcium signal alone is sufficient to mediate induction of the IL-21 in preactivated T lymphocytes and that this induction appears to result from specific NFAT binding...
  40. pmc Synergy of IL-21 and IL-15 in regulating CD8+ T cell expansion and function
    Rong Zeng
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Exp Med 201:139-48. 2005
    ..Thus, our studies reveal that IL-21 potently regulates CD8+ T cell expansion and effector function, primarily in a synergistic context with IL-15...
  41. ncbi request reprint STAT5A-deficient mice demonstrate a defect in granulocyte-macrophage colony-stimulating factor-induced proliferation and gene expression
    G M Feldman
    Division of Cytokine Biology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892 4555, USA
    Blood 90:1768-76. 1997
    ..These data suggest that the presence of STAT5A during the GM-CSF-induced assembly of STAT5 dimers is critical for the formation of competent transcription factors that are required for both gene expression and cell proliferation...
  42. ncbi request reprint Interleukin-2 receptor gamma chain mutation results in X-linked severe combined immunodeficiency in humans
    M Noguchi
    Section on Pulmonary and Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892
    Cell 73:147-57. 1993
    ..These results also have important implications for prenatal and postnatal diagnosis, carrier female detection, and gene therapy for XSCID...
  43. ncbi request reprint The molecular basis of X-linked severe combined immunodeficiency: the role of the interleukin-2 receptor gamma chain as a common gamma chain, gamma c
    W J Leonard
    Section on Pulmonary and Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892
    Immunol Rev 138:61-86. 1994
    ....
  44. ncbi request reprint Characterization of the human interleukin-2 receptor gamma chain gene
    M Noguchi
    Section of Pulmonary and Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892
    J Biol Chem 268:13601-8. 1993
    ..With this study, the organization of the genes encoding all three chains (alpha, beta, and gamma) of the IL-2 receptor has been determined and promoters for each identified...
  45. ncbi request reprint Restoration of lymphoid populations in a murine model of X-linked severe combined immunodeficiency by a gene-therapy approach
    M Lo
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health NIH, Bethesda, MD 20892 1674, USA
    Blood 94:3027-36. 1999
    ....
  46. ncbi request reprint Regulation of B cell differentiation and plasma cell generation by IL-21, a novel inducer of Blimp-1 and Bcl-6
    Katsutoshi Ozaki
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA
    J Immunol 173:5361-71. 2004
    ..Finally, BXSB-Yaa mice, which develop a systemic lupus erythematosus-like disease, have greatly elevated IL-21, suggesting a role for IL-21 in the development of autoimmune disease...
  47. pmc A role for thymic stromal lymphopoietin in CD4(+) T cell development
    Amin Al-Shami
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Exp Med 200:159-68. 2004
    ..Thus, as compared with other known cytokines, TSLP is distinctive in exhibiting a lineage preference for the expansion and survival of CD4(+) T cells...
  48. ncbi request reprint A critical role for IL-21 in regulating immunoglobulin production
    Katsutoshi Ozaki
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892 1674, USA
    Science 298:1630-4. 2002
    ..This suggests that these gammac-dependent cytokines may be those whose inactivation is primarily responsible for the B cell defect in humans with XSCID...
  49. pmc Functional cooperation of the interleukin-2 receptor beta chain and Jak1 in phosphatidylinositol 3-kinase recruitment and phosphorylation
    T S Migone
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892 1674, USA
    Mol Cell Biol 18:6416-22. 1998
    ..This is the first report of a PI 3-K-Jak1 interaction, and it implicates Jak1 in an essential IL-2 signaling pathway distinct from the activation of STAT proteins...
  50. pmc Analysis of interleukin-21-induced Prdm1 gene regulation reveals functional cooperation of STAT3 and IRF4 transcription factors
    Hyokjoon Kwon
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892, USA
    Immunity 31:941-52. 2009
    ..These results reveal broad cooperative gene regulation by STAT3 and IRF4...
  51. ncbi request reprint Viral FLIP impairs survival of activated T cells and generation of CD8+ T cell memory
    Zhengqi Wu
    Immunoregulation Unit, Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 172:6313-23. 2004
    ..Through this mechanism, vFLIP proteins expressed by T cell tropic viruses may impair the CD8(+) T cell immune responses directed against them...
  52. pmc IL-21 and T follicular helper cells
    Rosanne Spolski
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892 1674, USA
    Int Immunol 22:7-12. 2010
    ..Here, we review the role of IL-21 in the regulation of normal T(FH) development and function as well as in progression of autoimmune responses...
  53. pmc Cloning of a type I cytokine receptor most related to the IL-2 receptor beta chain
    K Ozaki
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892 1674, USA
    Proc Natl Acad Sci U S A 97:11439-44. 2000
    ..This finding suggests that NILR has signaling potential but that a full understanding of its signaling partner(s) is not yet clear. Like IL-2Rbeta, NILR associates with Jak1 and mediates Stat5 activation...
  54. pmc The human T-cell leukemia/lymphotropic virus type 1 p12I proteins bind the interleukin-2 receptor beta and gammac chains and affects their expression on the cell surface
    J C Mulloy
    Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, Maryland 20892, USA
    J Virol 70:3599-605. 1996
    ..The interactions of p12I with IL-2R beta and gamma(c) may have important implications in the immunosuppressive effect of HTLV-1 in vivo as well as in the ligand-independent HTLV-1-mediated T-cell proliferation...
  55. pmc The common cytokine receptor gamma chain plays an essential role in regulating lymphoid homeostasis
    H Nakajima
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892, USA
    J Exp Med 185:189-95. 1997
    ....
  56. pmc IL-21 mediates suppressive effects via its induction of IL-10
    Rosanne Spolski
    Laboratory of Molecular Immunology and Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 182:2859-67. 2009
    ..Overall, our data indicate that IL-21 regulates immune responses at least in part by inducing IL-10 and reveal unanticipated immunosuppressive actions for this cytokine...
  57. pmc IL-2 negatively regulates IL-7 receptor alpha chain expression in activated T lymphocytes
    Hai Hui Xue
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Building 10, Room 7N252, Bethesda, MD 20892 1674, USA
    Proc Natl Acad Sci U S A 99:13759-64. 2002
    ..Our findings now suggest a previously unknown type of cross-talk between IL-2 and IL-7 signaling by showing that IL-2 signaling can diminish IL-7Ralpha expression via a phosphatidylinositol 3-kinase/Akt-dependent mechanism...
  58. ncbi request reprint Mutation of Jak3 in a patient with SCID: essential role of Jak3 in lymphoid development
    S M Russell
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute NHLBI, National Institutes of Health NIH, Bethesda, MD 20892, USA
    Science 270:797-800. 1995
    ..These observations indicate that the functions of gamma c are dependent on Jak3 and that Jak3 is essential for lymphoid development and signaling...
  59. pmc Adoptively transferred effector cells derived from naive rather than central memory CD8+ T cells mediate superior antitumor immunity
    Christian S Hinrichs
    National Cancer Institute, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 106:17469-74. 2009
    ..These results indicate that insertion of genes that confer antitumor specificity into naïve rather than central memory CD8(+) T cells may allow superior efficacy upon adoptive transfer...
  60. pmc IL-2 and IL-21 confer opposing differentiation programs to CD8+ T cells for adoptive immunotherapy
    Christian S Hinrichs
    National Cancer Institute, Surgery Branch, National Institutes of Health, Bethesda, MD 20892 1502, USA
    Blood 111:5326-33. 2008
    ..Thus, the efficacy of CD8(+) T cells for adoptive immunotherapy can be influenced by opposing differentiation programs conferred by IL-2 and IL-21, a finding with important implications for the development of cellular cancer therapies...
  61. pmc A role for TSLP in the development of inflammation in an asthma model
    Amin Al-Shami
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Exp Med 202:829-39. 2005
    ..This underscores an important role for this cytokine in the development of inflammatory and/or allergic responses in vivo...
  62. pmc Interleukin-21 receptor gene induction in human T cells is mediated by T-cell receptor-induced Sp1 activity
    Zheng Wu
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood InstituteNational Institutes of Health, Building 10, Room 7N252, Bethesda, Maryland 20892 1674, USA
    Mol Cell Biol 25:9741-52. 2005
    ..These data indicate that TCR-induced IL-21R expression is driven by TCR-mediated augmentation of Sp1 protein levels and may partly depend on the dephosphorylation of Sp1...
  63. ncbi request reprint Smad-dependent cooperative regulation of interleukin 2 receptor alpha chain gene expression by T cell receptor and transforming growth factor-beta
    Hyoung Pyo Kim
    Laboratory of Molecular Immunology, NHLBI, National Institutes of Health, Bethesda, Maryland 20892 1674, USA
    J Biol Chem 280:34042-7. 2005
    ..These findings have implications related to IL-2Ralpha expression on activated T cells and regulatory T cells...
  64. ncbi request reprint Measurement of interleukin-21
    Rong Zeng
    National Institutes of Health, Bethesda, Maryland, USA
    Curr Protoc Immunol . 2007
    ..Finally, a method to assess IL-21-induced tyrosine phosphorylation of Stat3 in splenic CD8(+) T cells using a flow cytometry-based analysis is described...
  65. pmc IL-1 family members and STAT activators induce cytokine production by Th2, Th17, and Th1 cells
    Liying Guo
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 106:13463-8. 2009
    ....
  66. pmc CREB/ATF-dependent T cell receptor-induced FoxP3 gene expression: a role for DNA methylation
    Hyoung Pyo Kim
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Exp Med 204:1543-51. 2007
    ..Thus, T cell receptor-induced FoxP3 expression in T reg cells is controlled both by sequence-specific binding of CREB/ATF and by DNA methylation of a CpG island...
  67. ncbi request reprint A role for Stat5 in CD8+ T cell homeostasis
    John Kelly
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 170:210-7. 2003
    ..Moreover, CD8+ memory T cells are substantially affected by Stat5 levels. These findings identify Stat5 proteins as critical signaling mediators used by cytokines to regulate CD8+ T cell homeostasis...
  68. pmc The Yin and Yang of interleukin-21 in allergy, autoimmunity and cancer
    Rosanne Spolski
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892 1674, USA
    Curr Opin Immunol 20:295-301. 2008
    ..Moreover, IL-21 has potent anti-tumor effects and is implicated in the development of autoimmune diseases. Regulating IL-21 actions in vivo therefore has clinical potential for a range of diseases and is an area of active investigation...
  69. pmc Interleukin 21: a cytokine/cytokine receptor system that has come of age
    Warren J Leonard
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bldg 10, Rm 7B05, Bethesda, MD 20892 1674, USA
    J Leukoc Biol 84:348-56. 2008
    ..The ability to regulate and manipulate the actions of IL-21, therefore, has important implications for immunoregulation and the therapy of human disease...
  70. pmc The basis for TCR-mediated regulation of the IL-2 receptor alpha chain gene: role of widely separated regulatory elements
    Hyoung Pyo Kim
    Laboratory of Molecular Immunology, Building 10, Room 7N252, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
    EMBO J 21:3051-9. 2002
    ..Moreover, our data reveal a previously unappreciated link between the TCR-mediated up-regulation of the IL-2 and IL-2Ralpha genes...
  71. 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...
  72. ncbi request reprint Both integrated and differential regulation of components of the IL-2/IL-2 receptor system
    Hyoung Pyo Kim
    Laboratory of Molecular Immunology, Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892 1674, United States
    Cytokine Growth Factor Rev 17:349-66. 2006
    ..We now cover an under-reviewed area-the regulation of genes encoding IL-2 and IL-2R components, with an effort to integrate/explain this knowledge...
  73. ncbi request reprint IL-21 induces differentiation of human naive and memory B cells into antibody-secreting plasma cells
    Rachel Ettinger
    Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD 20892, USA
    J Immunol 175:7867-79. 2005
    ..Taken together, our data show that IL-21 plays a central role in CSR and plasma cell differentiation during T cell-dependent B cell responses...
  74. ncbi request reprint Functionally distinct NF-kappa B binding sites in the immunoglobulin kappa and IL-2 receptor alpha chain genes
    S L Cross
    Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, Bethesda, MD 20892
    Science 244:466-9. 1989
    ....
  75. ncbi request reprint Dysfunctional cytokine receptor signaling in severe combined immunodeficiency
    W J Leonard
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892 1674, USA
    J Investig Med 44:304-11. 1996
    ..Implicit in these findings are the exciting possibilities of gene therapy for XSCID and Jak3-deficient SCID, as well as the possibility that new immunosuppressive drugs might be based on the ability to disrupt Jak-STAT pathways...
  76. pmc Critical role for Rsk2 in T-lymphocyte activation
    Jian Xin Lin
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
    Blood 111:525-33. 2008
    ..These results indicate an essential nonredundant role of Rsk2 in T-cell activation...
  77. pmc Thymic stromal lymphopoietin: a new cytokine in asthma
    Yrina Rochman
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institute of Health, Building 10, Room 7B05, Bethesda, MD 20892, USA
    Curr Opin Pharmacol 8:249-54. 2008
    ..TSLP affects dendritic cells, T cells, NKT cells, and mast cells, indicative of the broad role of TSLP in the regulation of inflammatory/allergic processes...
  78. pmc Thymic stromal lymphopoietin-mediated STAT5 phosphorylation via kinases JAK1 and JAK2 reveals a key difference from IL-7-induced signaling
    Yrina Rochman
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892 1674, USA
    Proc Natl Acad Sci U S A 107:19455-60. 2010
    ..These findings clarify the basis for TSLP-mediated signaling and provide an example wherein a cytokine uses JAK1 and JAK2 to mediate the activation of STAT5...
  79. pmc New insights into the regulation of T cells by gamma(c) family cytokines
    Yrina Rochman
    National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892 1674, USA
    Nat Rev Immunol 9:480-90. 2009
    ..This knowledge potentially allows for the therapeutic manipulation of immune responses for the treatment of cancer, autoimmunity, allergic diseases and immunodeficiency, as well as for vaccine development...
  80. ncbi request reprint Cutting edge: direct action of thymic stromal lymphopoietin on activated human CD4+ T cells
    Irina Rochman
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 178:6720-4. 2007
    ..Moreover, TSLP increases the sensitivity of human CD4(+) T cells to low doses of IL-2, augmenting responsiveness of these cells to TCR engagement. Our results establish that human CD4(+) T cells are direct targets for TSLP...
  81. ncbi request reprint In vivo antitumor activity of interleukin 21 mediated by natural killer cells
    Gang Wang
    Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
    Cancer Res 63:9016-22. 2003
    ..Our study suggests that IL-21 has significant antitumor activity and may have therapeutic potentials as an antitumor agent in the clinic...
  82. ncbi request reprint GA binding protein regulates interleukin 7 receptor alpha-chain gene expression in T cells
    Hai Hui Xue
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Building 10, Room 7N252, Bethesda, Maryland 20892 1674, USA
    Nat Immunol 5:1036-44. 2004
    ....
  83. ncbi request reprint Cytokines and immunodeficiency diseases: critical roles of the gamma(c)-dependent cytokines interleukins 2, 4, 7, 9, 15, and 21, and their signaling pathways
    Panu E Kovanen
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892 1674, USA
    Immunol Rev 202:67-83. 2004
    ..We also briefly discuss other cytokines, such as interferon-gamma and IL-12, where mutations in the ligand or receptor or signaling components also cause clinical disease in humans...
  84. pmc Stat5 synergizes with T cell receptor/antigen stimulation in the development of lymphoblastic lymphoma
    John A Kelly
    Laboratory of Molecular Immunology, National Heart and Blood Institute, National Cancer Institute, Bethesda, MD 20892 1674, USA
    J Exp Med 198:79-89. 2003
    ..These data demonstrate the oncogenic potential of dysregulated expression of a STAT protein that is not constitutively activated, and that TCR stimulation can contribute to this process...
  85. ncbi request reprint Global analysis of IL-2 target genes: identification of chromosomal clusters of expressed genes
    Panu E Kovanen
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892 1674, USA
    Int Immunol 17:1009-21. 2005
    ..3, a region that contains genes encoding the tumor necrosis factor (TNF) superfamily members TNF, LT-alpha and LT-beta...
  86. ncbi request reprint Heterodimerization of the IL-2 receptor beta- and gamma-chain cytoplasmic domains is required for signalling
    Y Nakamura
    Section on Pulmonary and Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892
    Nature 369:330-3. 1994
    ..Finally, we provide a method for mapping residues in the gamma c cytoplasmic domain even in cells that constitutively express gamma c...
  87. ncbi request reprint Genetic mapping of the interleukin 1 receptor alpha and beta chain genes in the mouse
    C A Kozak
    Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892 0460, USA
    Mamm Genome 6:823-4. 1995
  88. ncbi request reprint Serine phosphorylation of Stat5 proteins in lymphocytes stimulated with IL-2
    Hai Hui Xue
    Laboratories of Molecular Immunology, National Heart, Lung and Blood Institute, NIH, Bethesda, MD 20892 USA
    Int Immunol 14:1263-71. 2002
    ....
  89. pmc T-cell development and function are modulated by dual specificity phosphatase DUSP5
    Panu E Kovanen
    Laboratory of Molecular Immunology, NHLBI, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 283:17362-9. 2008
    ..Thus, proper regulation of DUSP5 activity is critical for normal immune system development, IL-2 actions, and tolerance...
  90. ncbi request reprint Analysis of gamma c-family cytokine target genes. Identification of dual-specificity phosphatase 5 (DUSP5) as a regulator of mitogen-activated protein kinase activity in interleukin-2 signaling
    Panu E Kovanen
    Laboratory of Molecular Immunology, NHLBI, National Institutes of Health, Maryland 20892, USA
    J Biol Chem 278:5205-13. 2003
    ..Our findings provide insights into the shared versus distinctive actions by different members of the gamma(c) family of cytokines. Moreover, we have identified a DUSP5-dependent negative regulatory pathway for MAPK activity in T cells...
  91. pmc IL-21 signaling is critical for the development of type I diabetes in the NOD mouse
    Rosanne Spolski
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Building 10, Room 7B05, Bethesda, MD 20892 1674, USA
    Proc Natl Acad Sci U S A 105:14028-33. 2008
    ..Our studies establish a critical role for IL-21 in the development of type I diabetes in the NOD mouse, with obvious potential implications for type I diabetes in humans...
  92. pmc The IL-15 receptor {alpha} chain cytoplasmic domain is critical for normal IL-15Ralpha function but is not required for trans-presentation
    Zheng Wu
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892 1674, USA
    Blood 112:4411-9. 2008
    ..These experiments collectively indicate that IL-15Ralpha can act in cis in addition to acting in trans to present IL-15 to responding cells...
  93. ncbi request reprint High-resolution solution structure of the beta chemokine hMIP-1 beta by multidimensional NMR
    P J Lodi
    Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892
    Science 263:1762-7. 1994
    ..Calculation of the solvation free energies of dimerization suggests that the formation and stabilization of the two different types of dimers arise from the burial of hydrophobic residues...
  94. ncbi request reprint The gene encoding the Act-2 cytokine. Genomic structure, HTLV-I/Tax responsiveness of 5' upstream sequences, and chromosomal localization
    M Napolitano
    Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892
    J Biol Chem 266:17531-6. 1991
    ....
  95. ncbi request reprint Cytokine and cytokine receptor pleiotropy and redundancy
    Katsutoshi Ozaki
    Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892 1674, USA
    J Biol Chem 277:29355-8. 2002
  96. pmc Cytokine mediators of Th17 function
    Rosanne Spolski
    Laboratory of Molecular Immunology and Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethsda, MD, USA
    Eur J Immunol 39:658-61. 2009
    ..In this review, we discuss the current understanding of the specific functional characteristics and regulation of Th17 cytokines and clarify how they mediate the actions of Th17 cells...
  97. ncbi request reprint The transcription factor GABP is a critical regulator of B lymphocyte development
    Hai Hui Xue
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892 1674, USA
    Immunity 26:421-31. 2007
    ..GABP could bind to the regulatory regions of Pax5 and Cd79a in vivo. Thus, GABP is a key regulator of B cell development, maturation, and function...
  98. pmc Human interleukin 2 receptor beta-chain gene: chromosomal localization and identification of 5' regulatory sequences
    J R Gnarra
    Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892
    Proc Natl Acad Sci U S A 87:3440-4. 1990
    ..The IL-2R beta gene is localized to chromosome 22q11.2-q12, a region that is the locus for several lymphoid neoplasias...
  99. pmc Identification, cloning, and characterization of an immune activation gene
    M A Lipes
    Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, Bethesda, MD 20892
    Proc Natl Acad Sci U S A 85:9704-8. 1988
    ..Using a baculovirus expression system, we have shown that this gene encodes a secreted product. It is therefore possible that Act-2 represents a newly discovered cytokine...
  100. ncbi request reprint Overexpression of interleukin 21 induces expansion of hematopoietic progenitor cells
    Katsutoshi Ozaki
    Division of Hematopoietic Factors, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
    Int J Hematol 84:224-30. 2006
    ..These results demonstrate that IL-21 can induce the expansion of hematopoietic progenitor cells in vivo, even in the absence of mature T-cells and B-cells...
  101. pmc Thymic stromal lymphopoietin is not necessary or sufficient to mediate the thymopoietic effects of keratinocyte growth factor
    Martin Guimond
    Blood 111:969-70. 2008