Spolski R, Leonard WJ. Interleukin-21: a double-edged sword with therapeutic potential. Nat Rev Drug Discov. 2014;13:379–95.
Article
CAS
PubMed
Google Scholar
Korn T, Bettelli E, Gao W, Awasthi A, Jager A, Strom TB, et al. IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells. Nature. 2007;448:484–7.
Article
CAS
PubMed
PubMed Central
Google Scholar
Nurieva R, Yang XO, Martinez G, Zhang Y, Panopoulos AD, Ma L, et al. Essential autocrine regulation by IL-21 in the generation of inflammatory T cells. Nature. 2007;448:480–3.
Article
CAS
PubMed
Google Scholar
Nurieva RI, Chung Y, Hwang D, Yang XO, Kang HS, Ma L, et al. Generation of T follicular helper cells is mediated by interleukin-21 but independent of T helper 1, 2, or 17 cell lineages. Immunity. 2008;29:138–49.
Article
CAS
PubMed
PubMed Central
Google Scholar
Linterman MA, Beaton L, Yu D, Ramiscal RR, Srivastava M, Hogan JJ, et al. IL-21 acts directly on B cells to regulate Bcl-6 expression and germinal center responses. J Exp Med. 2010;207:353–63.
Article
CAS
PubMed
PubMed Central
Google Scholar
Zotos D, Coquet JM, Zhang Y, Light A, D’Costa K, Kallies A, et al. IL-21 regulates germinal center B cell differentiation and proliferation through a B cell-intrinsic mechanism. J Exp Med. 2010;207:365–78.
Article
CAS
PubMed
PubMed Central
Google Scholar
Ozaki K, Spolski R, Feng CG, Qi CF, Cheng J, Sher A, et al. A critical role for IL-21 in regulating immunoglobulin production. Science. 2002;298:1630–4.
Article
CAS
PubMed
Google Scholar
Jungel A, Distler JH, Kurowska-Stolarska M, Seemayer CA, Seibl R, Forster A, et al. Expression of interleukin-21 receptor, but not interleukin-21, in synovial fibroblasts and synovial macrophages of patients with rheumatoid arthritis. Arthritis Rheum. 2004;50:1468–76.
Article
PubMed
Google Scholar
Rasmussen TK, Andersen T, Hvid M, Hetland ML, Horslev-Petersen K, Stengaard-Pedersen K, et al. Increased interleukin 21 (IL-21) and IL-23 are associated with increased disease activity and with radiographic status in patients with early rheumatoid arthritis. J Rheumatol. 2010;37:2014–20.
Article
CAS
PubMed
Google Scholar
Niu X, He D, Zhang X, Yue T, Li N, Zhang JZ, et al. IL-21 regulates Th17 cells in rheumatoid arthritis. Hum Immunol. 2010;71:334–41.
Article
CAS
PubMed
Google Scholar
Liu R, Wu Q, Su D, Che N, Chen H, Geng L, et al. A regulatory effect of IL-21 on T follicular helper-like cell and B cell in rheumatoid arthritis. Arthritis Res Ther. 2012;14:R255.
Article
CAS
PubMed
PubMed Central
Google Scholar
Wang J, Shan Y, Jiang Z, Feng J, Li C, Ma L, et al. High frequencies of activated B cells and T follicular helper cells are correlated with disease activity in patients with new-onset rheumatoid arthritis. Clin Exp Immunol. 2013;174:212–20.
CAS
PubMed
PubMed Central
Google Scholar
Maiti AK, Kim-Howard X, Viswanathan P, Guillen L, Rojas-Villarraga A, Deshmukh H, et al. Confirmation of an association between rs6822844 at the Il2-Il21 region and multiple autoimmune diseases: evidence of a general susceptibility locus. Arthritis Rheum. 2010;62:323–9.
Article
CAS
PubMed
PubMed Central
Google Scholar
Terato K, Shimozuru Y, Katayama K, Takemitsu Y, Yamashita I, Miyatsu M, et al. Specificity of antibodies to type II collagen in rheumatoid arthritis. Arthritis Rheum. 1990;33:1493–500.
Article
CAS
PubMed
Google Scholar
He X, Kang AH, Stuart JM. Accumulation of T cells reactive to type II collagen in synovial fluid of patients with rheumatoid arthritis. J Rheumatol. 2000;27:589–93.
CAS
PubMed
Google Scholar
Brunsberg U, Gustafsson K, Jansson L, Michaelsson E, Ahrlund-Richter L, Pettersson S, et al. Expression of a transgenic class II Ab gene confers susceptibility to collagen-induced arthritis. Eur J Immunol. 1994;24:1698–702.
Article
CAS
PubMed
Google Scholar
Wooley PH, Luthra HS, Stuart JM, David CS. Type II collagen-induced arthritis in mice. I. Major histocompatibility complex (I region) linkage and antibody correlates. J Exp Med. 1981;154:688–700.
Article
CAS
PubMed
Google Scholar
Ranges GE, Sriram S, Cooper SM. Prevention of type II collagen-induced arthritis by in vivo treatment with anti-L3T4. J Exp Med. 1985;162:1105–10.
Article
CAS
PubMed
Google Scholar
Campbell IK, Hamilton JA, Wicks IP. Collagen-induced arthritis in C57BL/6 (H-2b) mice: new insights into an important disease model of rheumatoid arthritis. Eur J Immunol. 2000;30:1568–75.
Article
CAS
PubMed
Google Scholar
Svensson L, Jirholt J, Holmdahl R, Jansson L. B cell-deficient mice do not develop type II collagen-induced arthritis (CIA). Clin Exp Immunol. 1998;111:521–6.
Article
CAS
PubMed
PubMed Central
Google Scholar
Nakae S, Nambu A, Sudo K, Iwakura Y. Suppression of immune induction of collagen-induced arthritis in IL-17-deficient mice. J Immunol. 2003;171:6173–7.
Article
CAS
PubMed
Google Scholar
Lubberts E, Koenders MI, Oppers-Walgreen B, van den Bersselaar L, Coenen-de Roo CJ, Joosten LA, et al. Treatment with a neutralizing anti-murine interleukin-17 antibody after the onset of collagen-induced arthritis reduces joint inflammation, cartilage destruction, and bone erosion. Arthritis Rheum. 2004;50:650–9.
Article
CAS
PubMed
Google Scholar
Young DA, Hegen M, Ma HL, Whitters MJ, Albert LM, Lowe L, et al. Blockade of the interleukin-21/interleukin-21 receptor pathway ameliorates disease in animal models of rheumatoid arthritis. Arthritis Rheum. 2007;56:1152–63.
Article
CAS
PubMed
Google Scholar
Ryu JG, Lee J, Kim EK, Seo HB, Park JS, Lee SY, et al. Treatment of IL-21R-Fc control autoimmune arthritis via suppression of STAT3 signal pathway mediated regulation of the Th17/Treg balance and plasma B cells. Immunol Lett. 2015;163:143–50.
Article
CAS
PubMed
Google Scholar
Frentsch M, Arbach O, Kirchhoff D, Moewes B, Worm M, Rothe M, et al. Direct access to CD4+ T cells specific for defined antigens according to CD154 expression. Nat Med. 2005;11:1118–24.
Article
CAS
PubMed
Google Scholar
Block KE, Huang H. The cellular source and target of IL-21 in K/BxN autoimmune arthritis. J Immunol. 2013;191:2948–55.
Article
CAS
PubMed
PubMed Central
Google Scholar
Jang E, Cho SH, Park H, Paik DJ, Kim JM, Youn J. 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. J Immunol. 2009;182:4649–56.
Article
CAS
PubMed
Google Scholar
McPhee CG, Bubier JA, Sproule TJ, Park G, Steinbuck MP, Schott WH, et al. IL-21 is a double-edged sword in the systemic lupus erythematosus-like disease of BXSB.Yaa mice. J Immunol. 2013;191:4581–8.
Article
CAS
PubMed
Google Scholar
Zhou L, Ivanov II, Spolski R, Min R, Shenderov K, Egawa T, et al. IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat Immunol. 2007;8:967–74.
Article
CAS
PubMed
Google Scholar
Sonderegger I, Kisielow J, Meier R, King C, Kopf M. IL-21 and IL-21R are not required for development of Th17 cells and autoimmunity in vivo. Eur J Immunol. 2008;38:1833–8.
Article
CAS
PubMed
Google Scholar
Coquet JM, Chakravarti S, Smyth MJ, Godfrey DI. Cutting edge: IL-21 is not essential for Th17 differentiation or experimental autoimmune encephalomyelitis. J Immunol. 2008;180:7097–101.
Article
CAS
PubMed
Google Scholar
Takagi N, Mihara M, Moriya Y, Nishimoto N, Yoshizaki K, Kishimoto T, et al. Blockade of interleukin-6 receptor ameliorates joint disease in murine coaagen-induced arthritis. Arthritis Rheum. 1998;41:2117–21.
Article
CAS
PubMed
Google Scholar
Bessa J, Kopf M, Bachmann MF. Cutting edge: IL-21 and TLR signaling regulate germinal center responses in a B cell-intrinsic manner. J Immunol. 2010;184:4615–9.
Article
CAS
PubMed
Google Scholar
Crotty S. Follicular helper CD4 T cells (TFH). Annu Rev Immunol. 2011;29:621–63.
Article
CAS
PubMed
Google Scholar
Fazilleau N, McHeyzer-Williams LJ, Rosen H, McHeyzer-Williams MG. The function of follicular helper T cells is regulated by the strength of T cell antigen receptor binding. Nat Immunol. 2009;10:375–84.
Article
CAS
PubMed
PubMed Central
Google Scholar
Ignatenko S, Skrumsager BK, Mouritzen U. Safety, PK, and PD of recombinant anti-interleukin-21 monoclonal antibody in a first-in-human trial. Int J Clin Pharmacol Ther. 2016;54:243–52.
Article
PubMed
Google Scholar
Suwannalai P, van de Stadt LA, Radner H, Steiner G, El-Gabalawy HS, Zijde CM, et al. Avidity maturation of anti-citrullinated protein antibodies in rheumatoid arthritis. Arthritis Rheum. 2012;64:1323–8.
Article
CAS
PubMed
Google Scholar
Gerlag DM, Norris JM, Tak PP. Towards prevention of autoantibody-positive rheumatoid arthritis: from lifestyle modification to preventiive treatment. Rheumatology. 2016;55:607–14.
Article
PubMed
Google Scholar