Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Logo for

Science 298 (5598): 1630-1634

Copyright © 2002 by the American Association for the Advancement of Science

A Critical Role for IL-21 in Regulating Immunoglobulin Production

Katsutoshi Ozaki,1* Rosanne Spolski,1 Carl G. Feng,2 Chen-Feng Qi,3 Jun Cheng,4 Alan Sher,2 Herbert C. Morse III,3 Chengyu Liu,5 Pamela L. Schwartzberg,4 Warren J. Leonard1dagger

The cytokine interleukin-21 (IL-21) is closely related to IL-2 and IL-15, and their receptors all share the common cytokine receptor gamma  chain, gamma c, which is mutated in humans with X-linked severe combined immunodeficiency disease (XSCID). We demonstrate that, although mice deficient in the receptor for IL-21 (IL-21R) have normal lymphoid development, after immunization, these animals have higher production of the immunoglobulin IgE, but lower IgG1, than wild-type animals. Mice lacking both IL-4 and IL-21R exhibited a significantly more pronounced phenotype, with dysgammaglobulinemia, characterized primarily by a severely impaired IgG response. Thus, IL-21 has a significant influence on the regulation of B cell function in vivo and cooperates with IL-4. This suggests that these gamma c-dependent cytokines may be those whose inactivation is primarily responsible for the B cell defect in humans with XSCID.

1 Laboratory of Molecular Immunology,
5 Transgenic Facility, National Heart, Lung, and Blood Institute,
2 Laboratory of Parasitic Disease,
3 Laboratory of Immunopathology, National Institute of Allergy and Infectious Disease,
4 Genetic Disease Research Branch, National Human Genome Research Institute, Building 49, Room 4A38, National Institutes of Health, Bethesda, MD 20892-1674, USA.
*   Present address: Institute of Medical Science, University of Tokyo, Tokyo, Japan.

dagger    To whom correspondence should be addressed. E-mail: wjl{at}helix.nih.gov

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
IL-21-stimulated human plasmacytoid dendritic cells secrete granzyme B, which impairs their capacity to induce T-cell proliferation.
J. J. Karrich, L. C. M. Jachimowski, M. Nagasawa, A. Kamp, M. Balzarolo, M. C. Wolkers, C. H. Uittenbogaart, S. Marieke van Ham, and B. Blom (2013)
Blood 121, 3103-3111
   Abstract »    Full Text »    PDF »
Interleukin 21-Induced Granzyme B-Expressing B Cells Infiltrate Tumors and Regulate T Cells.
S. Lindner, K. Dahlke, K. Sontheimer, M. Hagn, C. Kaltenmeier, T. F. E. Barth, T. Beyer, F. Reister, D. Fabricius, R. Lotfi, et al. (2013)
Cancer Res. 73, 2468-2479
   Abstract »    Full Text »    PDF »
IL-21 Enhances Phagocytosis in Mononuclear Phagocyte Cells: Identification of Spleen Tyrosine Kinase as a Novel Molecular Target of IL-21.
F. Vallieres and D. Girard (2013)
J. Immunol. 190, 2904-2912
   Abstract »    Full Text »    PDF »
Loss-of-function mutations in the IL-21 receptor gene cause a primary immunodeficiency syndrome.
D. Kotlarz, N. Zietara, G. Uzel, T. Weidemann, C. J. Braun, J. Diestelhorst, P. M. Krawitz, P. N. Robinson, J. Hecht, J. Puchalka, et al. (2013)
J. Exp. Med. 210, 433-443
   Abstract »    Full Text »    PDF »
Regulatory B Cell (B10 Cell) Expansion during Listeria Infection Governs Innate and Cellular Immune Responses in Mice.
M. Horikawa, E. T. Weimer, D. J. DiLillo, G. M. Venturi, R. Spolski, W. J. Leonard, M. T. Heise, and T. F. Tedder (2013)
J. Immunol. 190, 1158-1168
   Abstract »    Full Text »    PDF »
Follicular helper T cells serve as the major CD4 T cell compartment for HIV-1 infection, replication, and production.
M. Perreau, A.-L. Savoye, E. De Crignis, J.-M. Corpataux, R. Cubas, E. K. Haddad, L. De Leval, C. Graziosi, and G. Pantaleo (2013)
J. Exp. Med. 210, 143-156
   Abstract »    Full Text »    PDF »
Paucity of IL-21-producing CD4+ T cells is associated with Th17 cell depletion in SIV infection of rhesus macaques.
L. Micci, B. Cervasi, Z. S. Ende, R. I. Iriele, E. Reyes-Aviles, C. Vinton, J. Else, G. Silvestri, A. A. Ansari, F. Villinger, et al. (2012)
Blood 120, 3925-3935
   Abstract »    Full Text »    PDF »
IL-21 in the bone marrow microenvironment contributes to IgM secretion and proliferation of malignant cells in Waldenstrom macroglobulinemia.
L. S. Hodge, S. C. Ziesmer, Z. Z. Yang, F. J. Secreto, M. A. Gertz, A. J. Novak, and S. M. Ansell (2012)
Blood 120, 3774-3782
   Abstract »    Full Text »    PDF »
B and T cells collaborate in antiviral responses via IL-6, IL-21, and transcriptional activator and coactivator, Oct2 and OBF-1.
A. Karnowski, S. Chevrier, G. T. Belz, A. Mount, D. Emslie, K. D'Costa, D. M. Tarlinton, A. Kallies, and L. M. Corcoran (2012)
J. Exp. Med. 209, 2049-2064
   Abstract »    Full Text »    PDF »
IL-21 Promotes Lupus-like Disease in Chronic Graft-versus-Host Disease through Both CD4 T Cell- and B Cell-Intrinsic Mechanisms.
V. Nguyen, I. Luzina, H. Rus, C. Tegla, C. Chen, and V. Rus (2012)
J. Immunol. 189, 1081-1093
   Abstract »    Full Text »    PDF »
IL-2 Requirement for Human Plasma Cell Generation: Coupling Differentiation and Proliferation by Enhancing MAPK-ERK Signaling.
S. Le Gallou, G. Caron, C. Delaloy, D. Rossille, K. Tarte, and T. Fest (2012)
J. Immunol. 189, 161-173
   Abstract »    Full Text »    PDF »
Delays and Diversions Mark the Development of B Cell Responses to Borrelia burgdorferi Infection.
C. J. Hastey, R. A. Elsner, S. W. Barthold, and N. Baumgarth (2012)
J. Immunol. 188, 5612-5622
   Abstract »    Full Text »    PDF »
Runx1 Deficiency in CD4+ T Cells Causes Fatal Autoimmune Inflammatory Lung Disease Due to Spontaneous Hyperactivation of Cells.
W. F. Wong, K. Kohu, A. Nakamura, M. Ebina, T. Kikuchi, R. Tazawa, K. Tanaka, S. Kon, T. Funaki, A. Sugahara-Tobinai, et al. (2012)
J. Immunol. 188, 5408-5420
   Abstract »    Full Text »    PDF »
CD80 Expression on B Cells Regulates Murine T Follicular Helper Development, Germinal Center B Cell Survival, and Plasma Cell Generation.
K. L. Good-Jacobson, E. Song, S. Anderson, A. H. Sharpe, and M. J. Shlomchik (2012)
J. Immunol. 188, 4217-4225
   Abstract »    Full Text »    PDF »
Bcl6 and Maf Cooperate To Instruct Human Follicular Helper CD4 T Cell Differentiation.
M. A. Kroenke, D. Eto, M. Locci, M. Cho, T. Davidson, E. K. Haddad, and S. Crotty (2012)
J. Immunol. 188, 3734-3744
   Abstract »    Full Text »    PDF »
Spatial Alterations between CD4+ T Follicular Helper, B, and CD8+ T Cells during Simian Immunodeficiency Virus Infection: T/B Cell Homeostasis, Activation, and Potential Mechanism for Viral Escape.
J. J. Hong, P. K. Amancha, K. Rogers, A. A. Ansari, and F. Villinger (2012)
J. Immunol. 188, 3247-3256
   Abstract »    Full Text »    PDF »
Crystal Structure of Interleukin-21 Receptor (IL-21R) Bound to IL-21 Reveals That Sugar Chain Interacting with WSXWS Motif Is Integral Part of IL-21R.
O. J. Hamming, L. Kang, A. Svensson, J. L. Karlsen, H. Rahbek-Nielsen, S. R. Paludan, S. A. Hjorth, K. Bondensgaard, and R. Hartmann (2012)
J. Biol. Chem. 287, 9454-9460
   Abstract »    Full Text »    PDF »
Increased Frequency of Follicular Helper T Cells in Patients with Autoimmune Thyroid Disease.
C. Zhu, J. Ma, Y. Liu, J. Tong, J. Tian, J. Chen, X. Tang, H. Xu, L. Lu, and S. Wang (2012)
J. Clin. Endocrinol. Metab. 97, 943-950
   Abstract »    Full Text »    PDF »
IL-21 Promotes the Pathologic Immune Response to Pneumovirus Infection.
R. Spolski, L. Wang, C.-K. Wan, C. A. Bonville, J. B. Domachowske, H.-P. Kim, Z. Yu, and W. J. Leonard (2012)
J. Immunol. 188, 1924-1932
   Abstract »    Full Text »    PDF »
IL-21 Receptor Is Required for the Systemic Accumulation of Activated B and T Lymphocytes in MRL/MpJ-Faslpr/lpr/J Mice.
A. L. Rankin, H. Guay, D. Herber, S. A. Bertino, T. A. Duzanski, Y. Carrier, S. Keegan, M. Senices, N. Stedman, M. Ryan, et al. (2012)
J. Immunol. 188, 1656-1667
   Abstract »    Full Text »    PDF »
Sequential class switching is required for the generation of high affinity IgE antibodies.
H. Xiong, J. Dolpady, M. Wabl, M. A. Curotto de Lafaille, and J. J. Lafaille (2012)
J. Exp. Med. 209, 353-364
   Abstract »    Full Text »    PDF »
SOCS3 Deletion in B Cells Alters Cytokine Responses and Germinal Center Output.
S. A. Jones, C. A. White, L. Robb, W. S. Alexander, and D. M. Tarlinton (2011)
J. Immunol. 187, 6318-6326
   Abstract »    Full Text »    PDF »
Alphavirus-Induced Encephalomyelitis: Antibody-Secreting Cells and Viral Clearance from the Nervous System.
T. U. Metcalf and D. E. Griffin (2011)
J. Virol. 85, 11490-11501
   Abstract »    Full Text »    PDF »
Regulation of the Germinal Center Reaction by Foxp3+ Follicular Regulatory T Cells.
I. Wollenberg, A. Agua-Doce, A. Hernandez, C. Almeida, V. G. Oliveira, J. Faro, and L. Graca (2011)
J. Immunol. 187, 4553-4560
   Abstract »    Full Text »    PDF »
IL-21-Dependent B Cell Death Driven by Prostaglandin E2, a Product Secreted from Follicular Dendritic Cells.
M. Magari, Y. Nishikawa, Y. Fujii, Y. Nishio, K. Watanabe, M. Fujiwara, N. Kanayama, and H. Ohmori (2011)
J. Immunol. 187, 4210-4218
   Abstract »    Full Text »    PDF »
Human tonsil B-cell lymphoma 6 (BCL6)-expressing CD4+ T-cell subset specialized for B-cell help outside germinal centers.
S.-E. Bentebibel, N. Schmitt, J. Banchereau, and H. Ueno (2011)
PNAS 108, E488-E497
   Abstract »    Full Text »    PDF »
Key role for IL-21 in experimental autoimmune uveitis.
L. Wang, C.-R. Yu, H.-P. Kim, W. Liao, W. G. Telford, C. E. Egwuagu, and W. J. Leonard (2011)
PNAS 108, 9542-9547
   Abstract »    Full Text »    PDF »
Facultative role for T cells in extrafollicular Toll-like receptor-dependent autoreactive B-cell responses in vivo.
R. A. Sweet, M. L. Ols, J. L. Cullen, A. V. Milam, H. Yagita, and M. J. Shlomchik (2011)
PNAS 108, 7932-7937
   Abstract »    Full Text »    PDF »
Viral persistence redirects CD4 T cell differentiation toward T follicular helper cells.
L. M. Fahey, E. B. Wilson, H. Elsaesser, C. D. Fistonich, D. B. McGavern, and D. G. Brooks (2011)
J. Exp. Med. 208, 987-999
   Abstract »    Full Text »    PDF »
Analysis of the Role of IL-21 in Development of Murine B Cell Progenitors in the Bone Marrow.
N. Simard, D. Konforte, A. H. Tran, J. Esufali, W. J. Leonard, and C. J. Paige (2011)
J. Immunol. 186, 5244-5253
   Abstract »    Full Text »    PDF »
IL-27 and IL-21 Are Associated with T Cell IL-10 Responses in Human Visceral Leishmaniasis.
N. A. Ansari, R. Kumar, S. Gautam, S. Nylen, O. P. Singh, S. Sundar, and D. Sacks (2011)
J. Immunol. 186, 3977-3985
   Abstract »    Full Text »    PDF »
Factors Supporting Intrathecal Humoral Responses following Viral Encephalomyelitis.
T. W. Phares, C. P. Marques, S. A. Stohlman, D. R. Hinton, and C. C. Bergmann (2011)
J. Virol. 85, 2589-2598
   Abstract »    Full Text »    PDF »
Interleukin-21 Is Critically Required in Autoimmune and Allogeneic Responses to Islet Tissue in Murine Models.
H. M. McGuire, S. Walters, A. Vogelzang, C. M. Y. Lee, K. E. Webster, J. Sprent, D. Christ, S. Grey, and C. King (2011)
Diabetes 60, 867-875
   Abstract »    Full Text »    PDF »
Intrinsic IL-21 Signaling Is Critical for CD8 T Cell Survival and Memory Formation in Response to Vaccinia Viral Infection.
P. Novy, X. Huang, W. J. Leonard, and Y. Yang (2011)
J. Immunol. 186, 2729-2738
   Abstract »    Full Text »    PDF »
CXCR4 Expression on Activated B Cells Is Downregulated by CD63 and IL-21.
N. Yoshida, D. Kitayama, M. Arima, A. Sakamoto, A. Inamine, H. Watanabe-Takano, M. Hatano, T. Koike, and T. Tokuhisa (2011)
J. Immunol. 186, 2800-2808
   Abstract »    Full Text »    PDF »
Metabolic Stress Boosts Humoral Responses In Vivo Independently of Inflammasome and Inflammatory Reaction.
F. Andris, S. Denanglaire, E. Baus, A. Rongvaux, J. Steuve, R. A. Flavell, and O. Leo (2011)
J. Immunol. 186, 2245-2253
   Abstract »    Full Text »    PDF »
IL-21 Receptor Is Critical for the Development of Memory B Cell Responses.
A. L. Rankin, H. MacLeod, S. Keegan, T. Andreyeva, L. Lowe, L. Bloom, M. Collins, C. Nickerson-Nutter, D. Young, and H. Guay (2011)
J. Immunol. 186, 667-674
   Abstract »    Full Text »    PDF »
Conserved natural IgM antibodies mediate innate and adaptive immunity against the opportunistic fungus Pneumocystis murina.
R. R. Rapaka, D. M. Ricks, J. F. Alcorn, K. Chen, S. A. Khader, M. Zheng, S. Plevy, E. Bengten, and J. K. Kolls (2010)
J. Exp. Med. 207, 2907-2919
   Abstract »    Full Text »    PDF »
IL-21 induces death of marginal zone B cells during chronic inflammation.
L. Tortola, K. Yadava, M. F. Bachmann, C. Muller, J. Kisielow, and M. Kopf (2010)
Blood 116, 5200-5207
   Abstract »    Full Text »    PDF »
A Nonredundant Role for IL-21 Receptor Signaling in Plasma Cell Differentiation and Protective Type 2 Immunity against Gastrointestinal Helminth Infection.
I. L. King, K. Mohrs, and M. Mohrs (2010)
J. Immunol. 185, 6138-6145
   Abstract »    Full Text »    PDF »
Plasticity and Heterogeneity in the Generation of Memory B Cells and Long-Lived Plasma Cells: The Influence of Germinal Center Interactions and Dynamics.
K. L. Good-Jacobson and M. J. Shlomchik (2010)
J. Immunol. 185, 3117-3125
   Abstract »    Full Text »    PDF »
B and T Lymphocyte Attenuator Suppresses IL-21 Production from Follicular Th Cells and Subsequent Humoral Immune Responses.
D. Kashiwakuma, A. Suto, Y. Hiramatsu, K. Ikeda, H. Takatori, K. Suzuki, S.-i. Kagami, K. Hirose, N. Watanabe, I. Iwamoto, et al. (2010)
J. Immunol. 185, 2730-2736
   Abstract »    Full Text »    PDF »
Proinflammatory T helper type 17 cells are effective B-cell helpers.
M. Mitsdoerffer, Y. Lee, A. Jager, H.-J. Kim, T. Korn, J. K. Kolls, H. Cantor, E. Bettelli, and V. K. Kuchroo (2010)
PNAS 107, 14292-14297
   Abstract »    Full Text »    PDF »
Altered Effector CD4+ T Cell Function in IL-21R-/- CD4+ T Cell-Mediated Graft-Versus-Host Disease.
I. Oh, K. Ozaki, A. Meguro, K. Hatanaka, M. Kadowaki, H. Matsu, R. Tatara, K. Sato, Y. Iwakura, S. Nakae, et al. (2010)
J. Immunol. 185, 1920-1926
   Abstract »    Full Text »    PDF »
Germinal Center T Follicular Helper Cell IL-4 Production Is Dependent on Signaling Lymphocytic Activation Molecule Receptor (CD150).
I. Yusuf, R. Kageyama, L. Monticelli, R. J. Johnston, D. DiToro, K. Hansen, B. Barnett, and S. Crotty (2010)
J. Immunol. 185, 190-202
   Abstract »    Full Text »    PDF »
In Vivo Regulation of Bcl6 and T Follicular Helper Cell Development.
A. C. Poholek, K. Hansen, S. G. Hernandez, D. Eto, A. Chandele, J. S. Weinstein, X. Dong, J. M. Odegard, S. M. Kaech, A. L. Dent, et al. (2010)
J. Immunol. 185, 313-326
   Abstract »    Full Text »    PDF »
Batf coordinates multiple aspects of B and T cell function required for normal antibody responses.
B. C. Betz, K. L. Jordan-Williams, C. Wang, S. G. Kang, J. Liao, M. R. Logan, C. H. Kim, and E. J. Taparowsky (2010)
J. Exp. Med. 207, 933-942
   Abstract »    Full Text »    PDF »
Cutting Edge: IL-21 and TLR Signaling Regulate Germinal Center Responses in a B Cell-Intrinsic Manner.
J. Bessa, M. Kopf, and M. F. Bachmann (2010)
J. Immunol. 184, 4615-4619
   Abstract »    Full Text »    PDF »
IL-21 regulates germinal center B cell differentiation and proliferation through a B cell-intrinsic mechanism.
D. Zotos, J. M. Coquet, Y. Zhang, A. Light, K. D'Costa, A. Kallies, L. M. Corcoran, D. I. Godfrey, K.-M. Toellner, M. J. Smyth, et al. (2010)
J. Exp. Med. 207, 365-378
   Abstract »    Full Text »    PDF »
IL-21 acts directly on B cells to regulate Bcl-6 expression and germinal center responses.
M. A. Linterman, L. Beaton, D. Yu, R. R. Ramiscal, M. Srivastava, J. J. Hogan, N. K. Verma, M. J. Smyth, R. J. Rigby, and C. G. Vinuesa (2010)
J. Exp. Med. 207, 353-363
   Abstract »    Full Text »    PDF »
B cell-intrinsic signaling through IL-21 receptor and STAT3 is required for establishing long-lived antibody responses in humans.
D. T. Avery, E. K. Deenick, C. S. Ma, S. Suryani, N. Simpson, G. Y. Chew, T. D. Chan, U. Palendira, J. Bustamante, S. Boisson-Dupuis, et al. (2010)
J. Exp. Med. 207, 155-171
   Abstract »    Full Text »    PDF »
Editorial: Memory CD8 T cells now join "Club 21".
Y. Tagaya (2010)
J. Leukoc. Biol. 87, 13-15
   Abstract »    Full Text »    PDF »
IL-21 and T follicular helper cells.
R. Spolski and W. J. Leonard (2010)
Int. Immunol. 22, 7-12
   Abstract »    Full Text »    PDF »
Interleukin-21 restores immunoglobulin production ex vivo in patients with common variable immunodeficiency and selective IgA deficiency.
S. Borte, Q. Pan-Hammarstrom, C. Liu, U. Sack, M. Borte, U. Wagner, D. Graf, and L. Hammarstrom (2009)
Blood 114, 4089-4098
   Abstract »    Full Text »    PDF »
TLR3 Ligand Polyinosinic:Polycytidylic Acid Induces IL-17A and IL-21 Synthesis in Human Th Cells.
C. K. Holm, C. C. Petersen, M. Hvid, L. Petersen, S. R. Paludan, B. Deleuran, and M. Hokland (2009)
J. Immunol. 183, 4422-4431
   Abstract »    Full Text »    PDF »
Modulation of Single-Cell IgG Secretion Frequency and Rates in Human Memory B Cells by CpG DNA, CD40L, IL-21, and Cell Division.
A. D. Henn, J. Rebhahn, M. A. Brown, A. J. Murphy, M. N. Coca, O. Hyrien, T. Pellegrin, T. Mosmann, and M. S. Zand (2009)
J. Immunol. 183, 3177-3187
   Abstract »    Full Text »    PDF »
IFN Regulatory Factor 8 Regulates MDM2 in Germinal Center B Cells.
J. X. Zhou, C. H. Lee, C. F. Qi, H. Wang, Z. Naghashfar, S. Abbasi, and H. C. Morse III (2009)
J. Immunol. 183, 3188-3194
   Abstract »    Full Text »    PDF »
IL-6 Is Required for Airway Mucus Production Induced by Inhaled Fungal Allergens.
W. A. Neveu, J. B. Allard, O. Dienz, M. J. Wargo, G. Ciliberto, L. A. Whittaker, and M. Rincon (2009)
J. Immunol. 183, 1732-1738
   Abstract »    Full Text »    PDF »
IL-21 Is Required to Control Chronic Viral Infection.
H. Elsaesser, K. Sauer, and D. G. Brooks (2009)
Science 324, 1569-1572
   Abstract »    Full Text »    PDF »
A Vital Role for Interleukin-21 in the Control of a Chronic Viral Infection.
J. S. Yi, M. Du, and A. J. Zajac (2009)
Science 324, 1572-1576
   Abstract »    Full Text »    PDF »
Suppression of murine SLE by oral anti-CD3: inducible CD4+CD25-LAP+ regulatory T cells control the expansion of IL-17+ follicular helper T cells.
H. Wu, E. Center, G. Tsokos, and H. Weiner (2009)
Lupus 18, 586-596
   Abstract »    PDF »
IL-21: a new player in the control of isotype switch in Peyer's patches.
V. Pistoia and C. Cocco (2009)
J. Leukoc. Biol. 85, 739-743
   Abstract »    Full Text »    PDF »
IL-21 ensures TGF-{beta}1-induced IgA isotype expression in mouse Peyer's patches.
G.-Y. Seo, J. Youn, and P.-H. Kim (2009)
J. Leukoc. Biol. 85, 744-750
   Abstract »    Full Text »    PDF »
Interleukin-21 Is Required for the Development of Type 1 Diabetes in NOD Mice.
A. P.R. Sutherland, T. Van Belle, A. L. Wurster, A. Suto, M. Michaud, D. Zhang, M. J. Grusby, and M. von Herrath (2009)
Diabetes 58, 1144-1155
   Abstract »    Full Text »    PDF »
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.
E. Jang, S.-H. Cho, H. Park, D.-J. Paik, J. M. Kim, and J. Youn (2009)
J. Immunol. 182, 4649-4656
   Abstract »    Full Text »    PDF »
Follicular helper T cells are required for systemic autoimmunity.
M. A. Linterman, R. J. Rigby, Raphael. K. Wong, D. Yu, R. Brink, J. L. Cannons, P. L. Schwartzberg, M. C. Cook, G. D. Walters, and C. G. Vinuesa (2009)
J. Exp. Med. 206, 561-576
   Abstract »    Full Text »    PDF »
Interleukin-6/STAT3 signaling regulates the ability of naive T cells to acquire B-cell help capacities.
F. Eddahri, S. Denanglaire, F. Bureau, R. Spolski, W. J. Leonard, O. Leo, and F. Andris (2009)
Blood 113, 2426-2433
   Abstract »    Full Text »    PDF »
IL-21 Mediates Suppressive Effects via Its Induction of IL-10.
R. Spolski, H.-P. Kim, W. Zhu, D. E. Levy, and W. J. Leonard (2009)
J. Immunol. 182, 2859-2867
   Abstract »    Full Text »    PDF »
IL-21: An Executor of B Cell Fate.
D. Konforte, N. Simard, and C. J. Paige (2009)
J. Immunol. 182, 1781-1787
   Abstract »    Full Text »    PDF »
A critical role for IL-21 receptor signaling in the pathogenesis of systemic lupus erythematosus in BXSB-Yaa mice.
J. A. Bubier, T. J. Sproule, O. Foreman, R. Spolski, D. J. Shaffer, H. C. Morse III, W. J. Leonard, and D. C. Roopenian (2009)
PNAS 106, 1518-1523
   Abstract »    Full Text »    PDF »
The induction of antibody production by IL-6 is indirectly mediated by IL-21 produced by CD4+ T cells.
O. Dienz, S. M. Eaton, J. P. Bond, W. Neveu, D. Moquin, R. Noubade, E. M. Briso, C. Charland, W. J. Leonard, G. Ciliberto, et al. (2009)
J. Exp. Med. 206, 69-78
   Abstract »    Full Text »    PDF »
Angiostatic activity of the antitumor cytokine interleukin-21.
K. Castermans, S. P. Tabruyn, R. Zeng, J. R. van Beijnum, C. Eppolito, W. J. Leonard, P. A. Shrikant, and A. W. Griffioen (2008)
Blood 112, 4940-4947
   Abstract »    Full Text »    PDF »
The IL-15 receptor {alpha} chain cytoplasmic domain is critical for normal IL-15R{alpha} function but is not required for trans-presentation.
Z. Wu, H.-H. Xue, J. Bernard, R. Zeng, D. Issakov, J. Bollenbacher-Reilley, I. M. Belyakov, S. Oh, J. A. Berzofsky, and W. J. Leonard (2008)
Blood 112, 4411-4419
   Abstract »    Full Text »    PDF »
Interleukin 21 as a target of intervention in autoimmune disease.
R Ettinger, S Kuchen, and P E Lipsky (2008)
Ann Rheum Dis 67, iii83-iii86
   Abstract »    Full Text »    PDF »
ICOS-dependent extrafollicular helper T cells elicit IgG production via IL-21 in systemic autoimmunity.
J. M. Odegard, B. R. Marks, L. D. DiPlacido, A. C. Poholek, D. H. Kono, C. Dong, R. A. Flavell, and J. Craft (2008)
J. Exp. Med. 205, 2873-2886
   Abstract »    Full Text »    PDF »
IL-21 Stimulates Human Myeloma Cell Growth through an Autocrine IGF-1 Loop.
E. Menoret, S. Maiga, G. Descamps, C. Pellat-Deceunynck, C. Fraslon, M. Cappellano, P. Moreau, R. Bataille, and M. Amiot (2008)
J. Immunol. 181, 6837-6842
   Abstract »    Full Text »    PDF »
The "Bubble Boy" Paradox: An Answer That Led to a Question.
L. J. Berg (2008)
J. Immunol. 181, 5815-5816
   Full Text »    PDF »
Nasal Anti-CD3 Antibody Ameliorates Lupus by Inducing an IL-10-Secreting CD4+CD25-LAP+ Regulatory T Cell and Is Associated with Down-Regulation of IL-17+CD4+ICOS+CXCR5+ Follicular Helper T Cells.
H. Y. Wu, F. J. Quintana, and H. L. Weiner (2008)
J. Immunol. 181, 6038-6050
   Abstract »    Full Text »    PDF »
Dissociation of Its Opposing Immunologic Effects Is Critical for the Optimization of Antitumor CD8+ T-Cell Responses Induced by Interleukin 21.
S. Ansen, M. O. Butler, A. Berezovskaya, A. P. Murray, K. Stevenson, L. M. Nadler, and N. Hirano (2008)
Clin. Cancer Res. 14, 6125-6136
   Abstract »    Full Text »    PDF »
IL-21 signaling is critical for the development of type I diabetes in the NOD mouse.
R. Spolski, M. Kashyap, C. Robinson, Z. Yu, and W. J. Leonard (2008)
PNAS 105, 14028-14033
   Abstract »    Full Text »    PDF »
STAT3 is required for IL-21-induced secretion of IgE from human naive B cells.
D. T. Avery, C. S. Ma, V. L. Bryant, B. Santner-Nanan, R. Nanan, M. Wong, D. A. Fulcher, M. C. Cook, and S. G. Tangye (2008)
Blood 112, 1784-1793
   Abstract »    Full Text »    PDF »
Interleukin 21: a cytokine/cytokine receptor system that has come of age.
W. J. Leonard, R. Zeng, and R. Spolski (2008)
J. Leukoc. Biol. 84, 348-356
   Abstract »    Full Text »    PDF »
IL-21 promotes survival and maintains a naive phenotype in human CD4+ T lymphocytes.
S. Ferrari-Lacraz, R. Chicheportiche, G. Schneiter, N. Molnarfi, J. Villard, and J.-M. Dayer (2008)
Int. Immunol. 20, 1009-1018
   Abstract »    Full Text »    PDF »
Targeting the GA Binding Protein {beta}1L Isoform Does Not Perturb Lymphocyte Development and Function.
H.-H. Xue, X. Jing, J. Bollenbacher-Reilley, D.-M. Zhao, J. S. Haring, B. Yang, C. Liu, G. A. Bishop, J. T. Harty, and W. J. Leonard (2008)
Mol. Cell. Biol. 28, 4300-4309
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882