Il21r

Summary

Gene Symbol: Il21r
Description: interleukin 21 receptor
Alias: NILR, interleukin-21 receptor, IL-21 receptor, IL-21R, LR-beta, NR8, lymphocyte receptor beta, novel cytokine receptor 8, novel interleukin receptor
Species: mouse

Top Publications

  1. ncbi IL-21 limits NK cell responses and promotes antigen-specific T cell activation: a mediator of the transition from innate to adaptive immunity
    Marion T Kasaian
    Genetics Institute, Wyeth Research, Cambridge, MA 02140, USA
    Immunity 16:559-69. 2002
  2. ncbi Distinct activation signals determine whether IL-21 induces B cell costimulation, growth arrest, or Bim-dependent apoptosis
    Haoli Jin
    Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, FL 33101, USA
    J Immunol 173:657-65. 2004
  3. pmc Development and characterization of IL-21-producing CD4+ T cells
    Akira Suto
    Department of Molecular Genetics, Graduate School of Medicine, Chiba University, Chiba, 260 8670 Japan
    J Exp Med 205:1369-79. 2008
  4. doi A positive feedback loop of IL-21 signaling provoked by homeostatic CD4+CD25- T cell expansion is essential for the development of arthritis in autoimmune K/BxN mice
    Eunkyeong Jang
    Department of Biomedical Sciences and Institute of Biomedical Sciences, College of Medicine, Hanyang University, Seoul, Korea
    J Immunol 182:4649-56. 2009
  5. pmc Altered effector CD4+ T cell function in IL-21R-/- CD4+ T cell-mediated graft-versus-host disease
    Iekuni Oh
    Division of Hematology, Department of Medicine, Jichi Medical University, Tochigi, Japan
    J Immunol 185:1920-6. 2010
  6. pmc IL-21 acts directly on B cells to regulate Bcl-6 expression and germinal center responses
    Michelle A Linterman
    John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia
    J Exp Med 207:353-63. 2010
  7. doi A fundamental role for interleukin-21 in the generation of T follicular helper cells
    Alexis Vogelzang
    Department of Immunology, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia
    Immunity 29:127-37. 2008
  8. pmc IL-21 limits peripheral lymphocyte numbers through T cell homeostatic mechanisms
    Shrimati Datta
    Department of Immunology, The Scripps Research Institute, La Jolla, California, United States of America
    PLoS ONE 3:e3118. 2008
  9. 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
  10. pmc Interleukin-21 is required for the development of type 1 diabetes in NOD mice
    Andrew P R Sutherland
    Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA
    Diabetes 58:1144-55. 2009

Research Grants

Scientific Experts

  • Anthony French
  • Christian S Hinrichs
  • Lan Liu
  • Nathalie Simard
  • Liu Wei
  • Andrew P R Sutherland
  • Deborah Herber
  • Warren J Leonard
  • Rosanne Spolski
  • Mark J Smyth
  • Jonathan M Coquet
  • Manfred Kopf
  • Helen M McGuire
  • Mary Collins
  • Vijay K Kuchroo
  • Michael J Grusby
  • Deborah Young
  • Irah L King
  • Alexis Vogelzang
  • Cecile King
  • Daisuke Kashiwakuma
  • John S Yi
  • Akira Suto
  • Anja Fröhlich
  • Ruolan Liu
  • Chi Keung Wan
  • Haoli Jin
  • Lu Wang
  • Deborah A Young
  • Hyoung Pyo Kim
  • Jason A Bubier
  • Allan J Zajac
  • Yukiko Hiramatsu
  • Shin ichiro Kagami
  • Norihiko Watanabe
  • Itsuo Iwamoto
  • Hiroshi Nakajima
  • Koichi Hirose
  • Caroline Pot
  • Jan Kisielow
  • Dale I Godfrey
  • Herbert C Morse
  • Ivo Sonderegger
  • Deepak Mittal
  • David E Levy
  • Caroline G McPhee
  • Sine K Kratholm
  • Harumichi Ishigame
  • Mohammed Ata Ur Rasheed
  • Filiberto Cedeno-Laurent
  • Kesley Attridge
  • Ayumi Yoshizaki
  • Vinh Nguyen
  • Tom L Van Belle
  • Wei Liu
  • Katsutoshi Ozaki
  • Alan M Hanash
  • Thomas J Sproule
  • Daniel Christ
  • Jie Sun
  • Alessandra Petrelli
  • Derry C Roopenian
  • Andrew L Rankin
  • Jean Publicover
  • Senta M Walton
  • Anneli Peters
  • Rebecca A Sweet
  • Nobuya Yoshida
  • Patricia Novy
  • Ram Savan
  • Markus Mohrs
  • Iekuni Oh
  • Geoffrey R Hill
  • Natalie N Whitfield
  • Martin F Bachmann
  • Yoichiro Iwakura
  • Michelle A Linterman
  • Brianne R Barker
  • Luigi Tortola
  • Lionel Apetoh
  • Zuxi Yu
  • Dimitra Zotos
  • Kei Ikeda
  • Annette Oxenius
  • Ming Du
  • Juliana Bessa
  • Jonathan Sprent
  • Christoph Bucher
  • Jeehee Youn
  • Estelle Bettelli

Detail Information

Publications83

  1. ncbi IL-21 limits NK cell responses and promotes antigen-specific T cell activation: a mediator of the transition from innate to adaptive immunity
    Marion T Kasaian
    Genetics Institute, Wyeth Research, Cambridge, MA 02140, USA
    Immunity 16:559-69. 2002
    ..These observations suggest that IL-21 promotes the transition between innate and adaptive immunity...
  2. ncbi Distinct activation signals determine whether IL-21 induces B cell costimulation, growth arrest, or Bim-dependent apoptosis
    Haoli Jin
    Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, FL 33101, USA
    J Immunol 173:657-65. 2004
    ..We favor a model in which IL-21 promotes B cell maturation during a productive T cell-dependent B cell response, while favoring growth arrest and apoptosis for nonspecifically or inappropriately activated B cells...
  3. pmc Development and characterization of IL-21-producing CD4+ T cells
    Akira Suto
    Department of Molecular Genetics, Graduate School of Medicine, Chiba University, Chiba, 260 8670 Japan
    J Exp Med 205:1369-79. 2008
    ....
  4. doi A positive feedback loop of IL-21 signaling provoked by homeostatic CD4+CD25- T cell expansion is essential for the development of arthritis in autoimmune K/BxN mice
    Eunkyeong Jang
    Department of Biomedical Sciences and Institute of Biomedical Sciences, College of Medicine, Hanyang University, Seoul, Korea
    J Immunol 182:4649-56. 2009
    ..Our findings suggest that effective targeting of IL-21-mediated processes may be useful in treating autoimmune arthritis...
  5. pmc Altered effector CD4+ T cell function in IL-21R-/- CD4+ T cell-mediated graft-versus-host disease
    Iekuni Oh
    Division of Hematology, Department of Medicine, Jichi Medical University, Tochigi, Japan
    J Immunol 185:1920-6. 2010
    ..Thus, the attenuated GVHD might be caused by an impairment of effector T cell differentiation itself, rather than by an increase in regulatory T cells and suppression of effector T cells...
  6. pmc IL-21 acts directly on B cells to regulate Bcl-6 expression and germinal center responses
    Michelle A Linterman
    John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia
    J Exp Med 207:353-63. 2010
    ..In contrast to the requirement for IL-21 in the follicular response to sheep red blood cells, a purely extrafollicular antibody response to Salmonella dominated by IgG2a was intact in the absence of IL-21...
  7. doi A fundamental role for interleukin-21 in the generation of T follicular helper cells
    Alexis Vogelzang
    Department of Immunology, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia
    Immunity 29:127-37. 2008
    ..This study reveals a previously unappreciated role for Tfh cells in the formation of the GC and isotype switching through a CD4(+) T cell-intrinsic requirement for IL-21...
  8. pmc IL-21 limits peripheral lymphocyte numbers through T cell homeostatic mechanisms
    Shrimati Datta
    Department of Immunology, The Scripps Research Institute, La Jolla, California, United States of America
    PLoS ONE 3:e3118. 2008
    ..IL-21, a member of the common gamma-chain utilizing family of cytokines, participates in immune and inflammatory processes. In addition, the cytokine has been linked to autoimmunity in humans and rodents...
  9. 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
    ..To determine the role of IL-21 in diabetes, Il21r-knockout (KO) mice were backcrossed to NOD mice...
  10. pmc Interleukin-21 is required for the development of type 1 diabetes in NOD mice
    Andrew P R Sutherland
    Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA
    Diabetes 58:1144-55. 2009
    ..The aim of this study was to investigate a causal role for IL-21 in type 1 diabetes...
  11. 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...
  12. pmc IL-21 is required to control chronic viral infection
    Heidi Elsaesser
    Department of Microbiology, Immunology, and Molecular Genetics and University of California, Los Angeles UCLA AIDS Institute, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA
    Science 324:1569-72. 2009
    ..Thus, IL-21 specifically sustains CD8+ T cell effector activity and provides a mechanism of CD4+ T cell help during chronic viral infection...
  13. pmc A vital role for interleukin-21 in the control of a chronic viral infection
    John S Yi
    Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294 2170, USA
    Science 324:1572-6. 2009
    ..Thus, IL-21 serves as a critical helper factor that shapes the functional quality of antiviral CD8+ T cells and is required for viral control...
  14. doi IL-21R on T cells is critical for sustained functionality and control of chronic viral infection
    Anja Fröhlich
    Molecular Biomedicine, Institute of Integrative Biology, ETH Zurich, Switzerland
    Science 324:1576-80. 2009
    Chronic viral infection is often associated with the dysfunction of virus-specific T cells. Our studies using Il21r-deficient (Il21r-/-) mice now suggest that interleukin-21 (IL-21) is critical for the long-term maintenance and ..
  15. pmc Cutting edge: IL-27 induces the transcription factor c-Maf, cytokine IL-21, and the costimulatory receptor ICOS that coordinately act together to promote differentiation of IL-10-producing Tr1 cells
    Caroline Pot
    Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Immunol 183:797-801. 2009
    ..ICOS further promotes IL-27-driven Tr1 cells. Each of those elements is essential, because loss of c-Maf, IL-21-signaling, or ICOS decreases the frequency of IL-27-induced differentiation of IL-10-producing Tr1 cells...
  16. pmc IL-21 blockade reduces graft-versus-host disease mortality by supporting inducible T regulatory cell generation
    Christoph Bucher
    University of Minnesota Cancer Center and Department of Pediatrics, Division of BMT, Minneapolis, MN, USA
    Blood 114:5375-84. 2009
    ..Together, these data indicate that IL-21 suppresses inducible Treg conversion and further suggest that IL-21 blockade is an attractive strategy to reduce GVHD-induced injury...
  17. ncbi Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function
    J Parrish-Novak
    Department of Functional Cloning, ZymoGenetics, Inc, Seattle, Washington 98102, USA
    Nature 408:57-63. 2000
    ....
  18. pmc IL-21 regulates germinal center B cell differentiation and proliferation through a B cell-intrinsic mechanism
    Dimitra Zotos
    The Walter and Eliza Hall Institute of Medical Research, Parkville 3052, Australia
    J Exp Med 207:365-78. 2010
    ..The absence of IL-21 or IL-21 receptor does not abrogate the appearance of T cells in GCs or the appearance of CD4 T cells with a follicular helper phenotype. IL-21 thus controls fate choices of GC B cells directly...
  19. doi Cutting edge: IL-21 and TLR signaling regulate germinal center responses in a B cell-intrinsic manner
    Juliana Bessa
    Cytos Biotechnology, Wagistrasse 25, Schlieren 8952, Switzerland
    J Immunol 184:4615-9. 2010
    ..Hence, IL-21 acts directly on B cells and cooperates with TLR signaling for optimal B cell responses...
  20. doi IL-21 receptor is critical for the development of memory B cell responses
    Andrew L Rankin
    Inflammation and Immunology, Pfizer Research, Cambridge, MA 02140, USA
    J Immunol 186:667-74. 2011
    ..KO mice, and consequently, secondary IgG Ab responses to NP hapten conjugated to chicken γ globulin were significantly impaired. These results identify the IL-21 pathway as a critical component of the memory B cell response...
  21. pmc Intrinsic IL-21 signaling is critical for CD8 T cell survival and memory formation in response to vaccinia viral infection
    Patricia Novy
    Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA
    J Immunol 186:2729-38. 2011
    ..These results identify a critical role for intrinsic IL-21 signaling in CD8 T cell responses to an acute viral infection in vivo and may help design effective vaccine strategies...
  22. pmc Interleukin-21 is critically required in autoimmune and allogeneic responses to islet tissue in murine models
    Helen M McGuire
    Department of Immunology, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia
    Diabetes 60:867-75. 2011
    ..In addition, we assessed the role of IL-21 responsiveness in islet allograft rejection in mouse animal models...
  23. pmc Key role for IL-21 in experimental autoimmune uveitis
    Lu Wang
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 108:9542-7. 2011
    ..Furthermore, Il21r(-/-) mice were more resistant to EAU development than wild-type mice, and adoptive transfer of Il21r(-/-) T cells ..
  24. pmc Abrogation of donor T-cell IL-21 signaling leads to tissue-specific modulation of immunity and separation of GVHD from GVL
    Alan M Hanash
    Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Blood 118:446-55. 2011
    ..IL-21 is thus an exciting target for therapeutic intervention and improvement of clinical transplantation outcomes...
  25. doi IL-21 inhibits T cell IL-2 production and impairs Treg homeostasis
    Kesley Attridge
    Medical Research Council Centre for Immune Regulation, University of Birmingham Medical School, Birmingham, UK
    Blood 119:4656-64. 2012
    ..The data also suggest a new paradigm whereby cytokines can promote immunity by inhibiting IL-2...
  26. pmc Interleukin-21 is a critical cytokine for the generation of virus-specific long-lived plasma cells
    Mohammed Ata Ur Rasheed
    Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA
    J Virol 87:7737-46. 2013
    ..Taken together, our results highlight the importance of IL-21 in humoral immunity to viruses...
  27. ncbi Cutting edge: IL-21 is not essential for Th17 differentiation or experimental autoimmune encephalomyelitis
    Jonathan M Coquet
    Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia
    J Immunol 180:7097-101. 2008
    ..Thus, our results challenge the notion that IL-21 is a key factor in driving Th17 immunity and disease...
  28. ncbi The common gamma chain (gamma c) is a required signaling component of the IL-21 receptor and supports IL-21-induced cell proliferation via JAK3
    Tania Habib
    Division of Hematology, University of Washington School of Medicine, Seattle, Washington 98195, USA
    Biochemistry 41:8725-31. 2002
    ....
  29. ncbi 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...
  30. 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...
  31. ncbi IL-21 receptor signaling is integral to the development of Th2 effector responses in vivo
    Anja Fröhlich
    Institute of Integrative Biology, Molecular Biomedicine, Swiss Federal Institute of Technology ETH Zurich, Switzerland
    Blood 109:2023-31. 2007
    ..Overall, our data show IL-21 plays a crucial role in supporting polarized Th2 responses in vivo, while appearing superfluous for Th1 and Th17 responses...
  32. ncbi IL-21 has a pathogenic role in a lupus-prone mouse model and its blockade with IL-21R.Fc reduces disease progression
    Deborah Herber
    Inflammation, Wyeth Research, 200 Cambridge Park Drive, Cambridge, MA 02140, USA
    J Immunol 178:3822-30. 2007
    ..From a clinical standpoint, these results suggest that blocking IL-21 in systemic lupus erythematosus patients may represent a promising novel therapeutic approach...
  33. ncbi 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...
  34. pmc IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells
    Thomas Korn
    Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 448:484-7. 2007
    ..We show that an IL-2 cytokine family member, IL-21, cooperates with TGF-beta to induce T(H)17 cells in naive Il6-/- T cells and that IL-21-receptor-deficient T cells are defective in generating a T(H)17 response...
  35. doi IL-21 and IL-21R are not required for development of Th17 cells and autoimmunity in vivo
    Ivo Sonderegger
    Institute of Integrative Biology, Molecular Biomedicine, ETH Zurich, Zurich, Switzerland
    Eur J Immunol 38:1833-8. 2008
    ..CD4 T cells, their recruitment to inflamed organs, and the development of autoimmune disease was not affected in il21R(-/-) and il21(-/-) mice in models of myelin oligodendrocyte glycoprotein-induced autoimmune encephalitis and ..
  36. 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
    We have identified a type I cytokine receptor, which we have termed novel interleukin receptor (NILR), that is most related to the IL-2 receptor beta chain (IL-2Rbeta) and physically adjacent to the IL-4 receptor alpha chain gene on ..
  37. doi Improved Treatment of Breast Cancer with Anti-HER2 Therapy Requires Interleukin-21 Signaling in CD8+ T Cells
    Deepak Mittal
    Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia School of Medicine, University of Queensland, Herston, Queensland, Australia
    Cancer Res 76:264-74. 2016
    ..of trastuzumab benefit on distant disease-free survival was higher for increasing expression of the IL21 receptor (IL21R). Therefore, we investigated a possible role for IL21 signaling in promoting HER2 mAb therapeutic efficacy...
  38. doi Interleukin-21-Producing CD4(+) T Cells Promote Type 2 Immunity to House Dust Mites
    Jonathan M Coquet
    VIB Inflammation Research Center IRC, Gent University, Zwijnaarde 9052B, Belgium Department of Microbiology, Tumor and Cell Biology MTC, Karolinska Institute, Stockholm 171 77, Sweden Electronic address
    Immunity 43:318-30. 2015
    ..b>Il21r(-/-) mice developed reduced type 2 responses and the IL-21 receptor (IL-21R) enhanced Th2 cell function in a cell-..
  39. pmc Interleukin-21 receptor signalling is important for innate immune protection against HSV-2 infections
    Sine K Kratholm
    Department of Biomedicine, Aarhus University, Aarhus, Denmark
    PLoS ONE 8:e81790. 2013
    ..Collectively our data demonstrate the novel finding that the IL-21R plays a critical role in regulating innate immune responses against HSV-2 infection. ..
  40. pmc IL-21 is a double-edged sword in the systemic lupus erythematosus-like disease of BXSB.Yaa mice
    Caroline G McPhee
    The Jackson Laboratory, Bar Harbor, ME 04609
    J Immunol 191:4581-8. 2013
    ..These results indicate that IL-21 has both disease-promoting and disease-suppressive effects in the autoimmune disease of BXSB.Yaa mice. ..
  41. pmc Excessive Th1 responses due to the absence of TGF-β signaling cause autoimmune diabetes and dysregulated Treg cell homeostasis
    Harumichi Ishigame
    Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
    Proc Natl Acad Sci U S A 110:6961-6. 2013
    ..These results indicate that autocrine/paracrine TGF-β signaling in diabetogenic CD4(+) T cells, but not Treg cells, is essential for controlling T1D development...
  42. pmc The aryl hydrocarbon receptor interacts with c-Maf to promote the differentiation of type 1 regulatory T cells induced by IL-27
    Lionel Apetoh
    Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA
    Nat Immunol 11:854-61. 2010
    ..Manipulating AhR signaling could therefore be beneficial in the resolution of excessive inflammatory responses...
  43. pmc The cytokines IL-21 and GM-CSF have opposing regulatory roles in the apoptosis of conventional dendritic cells
    Chi Keung Wan
    Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892 1674, USA
    Immunity 38:514-27. 2013
    ..CD4+ T cells caused more severe colitis with increased DCs and interferon-γ (IFN-γ)-producing CD4+ T cells in Il21r(-/-)Rag2(-/-) mice (which lack T cells and have IL-21-unresponsive DCs) than in Rag2(-/-) mice...
  44. pmc IL-21 is an antitolerogenic cytokine of the late-phase alloimmune response
    Alessandra Petrelli
    Transplantation Research Center, Children s Hospital, Harvard Medical School, Boston, Massachusetts, USA
    Diabetes 60:3223-34. 2011
    ..Interleukin-21 (IL-21) is a proinflammatory cytokine that has been shown to affect Treg/Teff balance. However, the mechanism by which IL-21 orchestrates alloimmune response and interplays with Tregs is still unclear...
  45. pmc Invariant natural killer T cells direct B cell responses to cognate lipid antigen in an IL-21-dependent manner
    Irah L King
    Trudeau Institute, Saranac Lake, New York, USA
    Nat Immunol 13:44-50. 2011
    ..Thus, cognate iNKT cell help for lipid-specific B cells induces a unique signature that is a hybrid of classic T cell-dependent and T cell-independent type 2 B cell responses...
  46. pmc IL-21R expression on CD8+ T cells promotes CD8+ T cell activation in coxsackievirus B3 induced myocarditis
    Wei Liu
    The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Harbin, Heilongjiang Province, 150001, China
    Exp Mol Pathol 92:327-33. 2012
    ..These data demonstrate that IL-21 signaling directly in the CD8+ cell population is required for CVB3-induced myocarditis...
  47. pmc IL-21 promotes the pathologic immune response to pneumovirus infection
    Rosanne Spolski
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 188:1924-32. 2012
    ..We found that PVM-infected mice expressed IL-21 in lung CD4(+) T cells. Following infection, Il21r(-/-) mice exhibited less lung infiltration by neutrophils than did wild-type (WT) mice and correspondingly had ..
  48. pmc Galectin-1 triggers an immunoregulatory signature in Th cells functionally defined by IL-10 expression
    Filiberto Cedeno-Laurent
    Department of Dermatology, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Immunol 188:3127-37. 2012
    ..Collectively, these findings show how Gal-1 functions as a major glycome determinant regulating Th cell development, inflammation, and tumor immunity...
  49. pmc Interleukin-21 receptor-mediated signals control autoreactive T cell infiltration in pancreatic islets
    Tom L Van Belle
    Type 1 Diabetes Center, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA
    Immunity 36:1060-72. 2012
    ..antigen, major histocompatibility complex (MHC) class II, and CD86 was provided to autoreactive effector cells in Il21r(-/-) mice, impairing CD4(+) T cell activation, CD40:CD40L interactions, and pancreatic infiltration by ..
  50. pmc IL-21 promotes lupus-like disease in chronic graft-versus-host disease through both CD4 T cell- and B cell-intrinsic mechanisms
    Vinh Nguyen
    Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA
    J Immunol 189:1081-93. 2012
    ....
  51. pmc Th17 cells induce ectopic lymphoid follicles in central nervous system tissue inflammation
    Anneli Peters
    Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Immunity 35:986-96. 2011
    ..Thus, Th17 cells are uniquely endowed to induce tissue inflammation, characterized by ectopic lymphoid follicles within the target organ...
  52. pmc Regulatory B cells control T-cell autoimmunity through IL-21-dependent cognate interactions
    Ayumi Yoshizaki
    Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Nature 491:264-8. 2012
    ..The ex vivo expansion and reinfusion of autologous B10 cells may provide a novel and effective in vivo treatment for severe autoimmune diseases that are resistant to current therapies...
  53. pmc IL-21 is pivotal in determining age-dependent effectiveness of immune responses in a mouse model of human hepatitis B
    Jean Publicover
    Department of Medicine, UCSF, San Francisco, California, USA
    J Clin Invest 121:1154-62. 2011
    ..These findings carry implications for therapeutic augmentation of immune responses to HBV and potentially other persistent liver viruses...
  54. ncbi STAT3 is a negative regulator of granulopoiesis but is not required for G-CSF-dependent differentiation
    Chien Kuo Lee
    Department of Pathology, Kaplan Comprehensive Cancer Center, New York University School of Medicine, 10016, USA
    Immunity 17:63-72. 2002
    ....
  55. doi T-cell help permits memory CD8(+) T-cell inflation during cytomegalovirus latency
    Senta M Walton
    Institute of Microbiology, ETH Zurich, Zurich, Switzerland
    Eur J Immunol 41:2248-59. 2011
    ..Thus, CD8(+) T-cell inflation during latent CMV infection is strongly dependent on CD4(+) T-cell helper functions, which can partially be compensated by ongoing lytic viral replication in the absence of CD4(+) T cells...
  56. pmc Facultative role for T cells in extrafollicular Toll-like receptor-dependent autoreactive B-cell responses in vivo
    Rebecca A Sweet
    Department of Immunobiology and Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520, USA
    Proc Natl Acad Sci U S A 108:7932-7. 2011
    ....
  57. doi A subset of interleukin-21+ chemokine receptor CCR9+ T helper cells target accessory organs of the digestive system in autoimmunity
    Helen M McGuire
    Department of Immunology, The Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia
    Immunity 34:602-15. 2011
    ..Thus, CCR9+ Th cells are a subset of IL-21-producing T helper cells that influence regional specification of autoimmune diseases that affect accessory organs of the digestive system...
  58. doi B and T lymphocyte attenuator suppresses IL-21 production from follicular Th cells and subsequent humoral immune responses
    Daisuke Kashiwakuma
    Department of Molecular Genetics, Graduate School of Medicine, Chiba University, Japan
    J Immunol 185:2730-6. 2010
    ..These results suggest that BTLA signaling suppresses IL-21 production from Tfh cells and subsequent Tfh cell-mediated IgG responses...
  59. 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...
  60. pmc Mouse macrophages are permissive to motile Legionella species that fail to trigger pyroptosis
    Natalie N Whitfield
    Cellular and Molecular Biology Program, University of Michigan Medical School, Ann Arbor, Michigan, USA
    Infect Immun 78:423-32. 2010
    ..These results point to the complexity of disease, a product of the pathogenic potential of the microbe, as defined in the laboratory, and the capacity of the host to mount a measured defense...
  61. doi IL-21 receptor expression determines the temporal phases of experimental autoimmune encephalomyelitis
    Ruolan Liu
    Department of Neurology, Barrow Neurological Institute, St Joseph s Hospital and Medical Center, 350 West Thomas Road, Phoenix, AZ 85013, USA
    Exp Neurol 211:14-24. 2008
    ..These results suggest that a temporal influence of IL-21 on the activity of immunoregulatory circuits can be important in the modulation of the course of the autoimmune disease...
  62. doi Endogenous IL-21 restricts CD8+ T cell expansion and is not required for tumor immunity
    Henrik Søndergaard
    Cancer Immunology Program, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia
    J Immunol 183:7326-36. 2009
    ....
  63. pmc Upregulated IL-21 and IL-21 receptor expression is involved in experimental autoimmune uveitis (EAU)
    Lan Liu
    Department of Ophthalmology, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, P R China
    Mol Vis 15:2938-44. 2009
    ..Our study is designed to investigate the alteration and possible function of IL-21 in the development of an experimental autoimmune uveitis (EAU) model...
  64. pmc The impact of T cell intrinsic antigen adaptation on peripheral immune tolerance
    Nevil J Singh
    Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
    PLoS Biol 4:e340. 2006
    ..These extrinsic mechanisms prevented the effector differentiation of the autoreactive T cells and reduced their precursor frequency, in vivo...
  65. ncbi DAP12 signaling directly augments proproliferative cytokine stimulation of NK cells during viral infections
    Anthony R French
    Division of Pediatric Rheumatology, Department of Pediatrics, Washington University School of Medicine, St Louis, MO 63110, USA
    J Immunol 177:4981-90. 2006
    ..The impact of Ly49H-mediated signaling on NK cell proliferation is masked in the presence of high concentrations of proproliferative cytokines that nonselectively drive all NK cells to proliferate...
  66. pmc The IL-21 receptor augments Th2 effector function and alternative macrophage activation
    John Pesce
    Immunopathogenesis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases NIAID, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Clin Invest 116:2044-55. 2006
    ..Collectively, these results illustrate an essential function for the IL-21R in the development of pathogen-induced Th2 responses, which may have relevance in therapies for both inflammatory and chronic fibrotic diseases...
  67. doi Stem cell mobilization with G-CSF induces type 17 differentiation and promotes scleroderma
    Geoffrey R Hill
    Queensland Institute of Medical Research, Brisbane, Australia
    Blood 116:819-28. 2010
    ..This study provides a logical explanation for the propensity of allogeneic stem cell transplantation to invoke sclerodermatous GVHD and suggests a therapeutic strategy for intervention...
  68. ncbi Autoreactive T cells mediate NK cell degeneration in autoimmune disease
    Ruolan Liu
    Barrow Neurological Institute, St Joseph s Hospital and Medical Center, 350 West Thomas Road, Phoenix, AZ 85013, USA
    J Immunol 176:5247-54. 2006
    ..Thus, NK cell degeneration may serve as a means evolved by the immune system to control excessive autoimmunity...
  69. pmc Analysis of the role of IL-21 in development of murine B cell progenitors in the bone marrow
    Nathalie Simard
    Ontario Cancer Institute, Princess Margaret Hospital, University Health Network, Toronto, Ontario M5G 2M9, Canada
    J Immunol 186:5244-53. 2011
    ..We also report in this paper that IL-21 is expressed by BM CD4(+) T cells. These results provide evidence that IL-21R is functional in B cell progenitors and indicate that IL-21 regulates B cell development...
  70. doi IL-21 induces death of marginal zone B cells during chronic inflammation
    Luigi Tortola
    Institute of Integrative Biology, Molecular Biomedicine, Eidgenossische Technische Hochschule Zurich, Schlieren, Switzerland
    Blood 116:5200-7. 2010
    ..Our results highlight key roles of IL-2 in inhibiting IL-21 production by CD4(+) T cells and of IL-21 in negatively regulating MZ B-cell survival and antibody production...
  71. pmc IL-21 deficiency influences CD8 T cell quality and recall responses following an acute viral infection
    John S Yi
    Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
    J Immunol 185:4835-45. 2010
    ..Collectively, these studies highlight the potential roles of IL-21 in determining the quality of CD8 T cell responses postinfection...
  72. pmc A nonredundant role for IL-21 receptor signaling in plasma cell differentiation and protective type 2 immunity against gastrointestinal helminth infection
    Irah L King
    Trudeau Institute, Saranac Lake, NY 12983, USA
    J Immunol 185:6138-45. 2010
    ..Our studies demonstrate a selective role for IL-21 in plasma cell differentiation in the context of protective antiparasitic type 2 immunity...
  73. pmc A novel role for IL-22R1 as a driver of inflammation
    Ram Savan
    Cancer and Inflammation Program, Center for Cancer Research, Frederick, MD, USA
    Blood 117:575-84. 2011
    ..This study documents a previously unknown role of IL-22R1 in inflammation and identifies the involvement of IL-22R1/IL-22 in ALK(+)ALCL...
  74. pmc Critical role for IL-21 in both primary and memory anti-viral CD8+ T-cell responses
    Brianne R Barker
    Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
    Eur J Immunol 40:3085-96. 2010
    ..These findings indicate that IL-21 is an important mediator of CD4(+) T-cell help to CD8(+) T cells...
  75. doi IL-21 ensures TGF-beta 1-induced IgA isotype expression in mouse Peyer's patches
    Goo Young Seo
    Department of Molecular Bioscience, School of Bioscience and Biotechnology, Kangwon National University, Chuncheon 200 701, Korea
    J Leukoc Biol 85:744-50. 2009
    ..Our results showed that IL-21 was expressed in greater magnitude in Peyer's patches (PP) than in spleen. These results suggest that IL-21 has an important effect on selective IgA(+) B cell commitment in PP...
  76. pmc A critical role for IL-21 receptor signaling in the pathogenesis of systemic lupus erythematosus in BXSB-Yaa mice
    Jason A Bubier
    The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA
    Proc Natl Acad Sci U S A 106:1518-23. 2009
    ..IL-21 arising from an abnormal population of CD4 T cells is thus central to the development of this lethal disease, and, more generally, could play an important role in human SLE and related autoimmune disorders...
  77. doi CXCR4 expression on activated B cells is downregulated by CD63 and IL-21
    Nobuya Yoshida
    Department of Developmental Genetics, H2, Graduate School of Medicine, Chiba University, Chiba 260 8670, Japan
    J Immunol 186:2800-8. 2011
    ..Thus, CXCR4 can be downregulated on activated B cells by IL-21-induced endocytosis and CD63-mediated endosomal recruitment, and these mechanisms may contribute to downregulation of CXCR4 on centrocytes...
  78. pmc CD4+ T cell help and innate-derived IL-27 induce Blimp-1-dependent IL-10 production by antiviral CTLs
    Jie Sun
    The Beirne B Carter Center for Immunology Research, The University of Virginia, Charlottesville, Virginia, USA
    Nat Immunol 12:327-34. 2011
    ..These findings reveal a previously unrecognized pathway that coordinates signals derived from innate and helper T cells to control the production of a regulatory cytokine by CTLs during acute viral infection...
  79. pmc IL-21R is essential for epicutaneous sensitization and allergic skin inflammation in humans and mice
    Haoli Jin
    Division of Immunology, Children s Hospital and Harvard Medical School, Boston, MA 02115, USA
    J Clin Invest 119:47-60. 2009
    ..The importance of this finding was highlighted by the fact that both Il21r-/- mice and WT mice treated with soluble IL-21R-IgG2aFc fusion protein failed to develop skin inflammation after e...
  80. ncbi Treatment of BXSB-Yaa mice with IL-21R-Fc fusion protein minimally attenuates systemic lupus erythematosus
    J A Bubier
    The Jackson Laboratory, 600 Main St Bar Harbor, ME 04609, USA
    Ann N Y Acad Sci 1110:590-601. 2007
    ..This experiment provides preliminary evidence for a role of IL-21 in modulating the severity of SLE in BXSB-Yaa mice...
  81. doi c-Maf activates the promoter and enhancer of the IL-21 gene, and TGF-beta inhibits c-Maf-induced IL-21 production in CD4+ T cells
    Yukiko Hiramatsu
    Department of Molecular Genetics, Graduate School of Medicine, Chiba University, Chiba 260 8670, Japan
    J Leukoc Biol 87:703-12. 2010
    ..Taken together, these results suggest that c-Maf induces IL-21 production directly in CD4(+) T cells by activating IL-21P and the CNS-2 enhancer and that TGF-beta suppresses c-Maf-induced IL-21 production in CD4(+) T cells...

Research Grants1

  1. Natural Killer Cell Mediated Control of Vaccinia Virus
    Anthony French; Fiscal Year: 2007
    ..The proposed work will occur under the mentorship of Dr. Wayne Yokoyama a recognized pioneer in the NK cell field who has successfully trained numerous graduate students and postdoctoral fellows. [unreadable] [unreadable]..