Targeting interleukin-21 in rheumatoid arthritis.
Interleukin-21 (IL-21) is a new member of the type I cytokine superfamily, which binds to a composite receptor that consists of a private receptor (IL-21R) and the common cytokine receptor γ chain. Recently, increasing evidence has shown that IL-21 contributes to the pathogenesis of chronic inflammatory and autoimmune diseases because of its pro-inflammatory and immune-mediated properties. IL-21 induced T-cell activation and pro-inflammatory cytokine secretion in rheumatoid arthritis (RA). IL-21R RNA transcripts were found in synovial tissue samples of patients with RA. In addition, blockade of the IL-21/IL-21R pathway ameliorated disease in animal models of RA and significantly inhibited inflammatory cytokine production in vitro. Moreover, IL-21R deficiency in the K/BxN mouse model of inflammatory arthritis was sufficient to block arthritis initiation completely. All theses findings suggest that IL-21 has important biological effects in autoimmunity that might be a promising therapeutic target for RA. In this review, we discuss the biological features of IL-21 and summarize recent advances in the role of IL-21 in the pathogenesis and treatment of RA.
Yuan
Feng-Lai
FL
The Third Hospital Affiliated to Nantong University, Wuxi, 214041 Jiangsu, People's Republic of China.
Hu
Wei
W
Lu
Wei-Guo
WG
Li
Xia
X
Li
Jian-Ping
JP
Xu
Rui-Sheng
RS
Li
Cheng-Wan
CW
Chen
Fei-Hu
FH
Jin
Cheng
C
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000628:therapy; D006801:Humans; D007378:Interleukins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D053655:Receptors, Interleukin-21 / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D000098546:Interleukin-21
D007378:Interleukins; D053655:Receptors, Interleukin-21; D000098546:Interleukin-21