Inducible costimulator is essential for collagen-induced arthritis
Roza I. Nurieva, … , Richard A. Flavell, Chen Dong
Roza I. Nurieva, … , Richard A. Flavell, Chen Dong
Published March 1, 2003
Citation Information: J Clin Invest. 2003;111(5):701-706. https://doi.org/10.1172/JCI17321.
View: Text | PDF | Retraction
Article Autoimmunity

Inducible costimulator is essential for collagen-induced arthritis

Abstract

CD4+ helper Th cells play a major role in the pathogenesis of rheumatoid arthritis. Th cell activation, differentiation, and immune function are regulated by costimulatory molecules. Inducible costimulator (ICOS) is a novel costimulatory receptor expressed on activated T cells. We, as well as others, recently demonstrated its importance in Th2 cytokine expression and Ab class switching by B cells. In this study, we examined the role of ICOS in rheumatoid arthritis using a collagen-induced arthritis model. We found that ICOS knockout mice on the DBA/1 background were completely resistant to collagen-induced arthritis and exhibited absence of joint tissue inflammation. These mice, when immunized with collagen, exhibited reduced anti-collagen IgM Ab’s in the initial stage and IgG2a Ab’s at the effector phase of collagen-induced arthritis. Furthermore, ICOS regulates the in vitro and in vivo expression of IL-17, a proinflammatory cytokine implicated in rheumatoid arthritis. These data indicate that ICOS is essential for collagen-induced arthritis and may suggest novel means for treating patients with rheumatoid arthritis.

Authors

Roza I. Nurieva, Piper Treuting, Julie Duong, Richard A. Flavell, Chen Dong

×

Figure 3

Options: View larger image (or click on image) Download as PowerPoint
Immunized ICOS–/– mice exhibited greatly reduced levels of anti-collagen...
Immunized ICOS–/– mice exhibited greatly reduced levels of anti-collagen IgM and IgG2a compared to ICOS+/+ mice. Anti-collagen Ab’s (IgM and IgG2a) were measured in the sera by ELISA. The sera from ICOS+/+ and ICOS–/– mice (three mice in each group), either 14 days after the first immunization or at the end of the experiment (day 58), were subjected to a threefold serial dilution; the concentrations of collagen-specific IgM and Ig2a were analyzed by ELISA, and average OD reading was indicated.