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.
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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

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Figure 1

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Resistance to collagen-induced arthritis by ICOS-deficient mice. ICOS–/–...
Resistance to collagen-induced arthritis by ICOS-deficient mice. ICOS–/– and ICOS+/+ mice on DBA/1 background were immunized at the base of the tail on days 0, 21, and 42 with type II chicken collagen in CFA. (a) Disease severity was scored on days 38, 42, 47, 48, 50, 55, and 58 by visual inspection of mouse paws. Each paw was scored for the degree of inflammation on a scale 0–4 as indicated in Methods. Scores were then added together. The data shown are a representative of two experiments on a total of more than ten mice in each group, with similar results. (b) Representative photos of forepaws and hindpaws of ICOS+/+ and ICOS–/– mice 58 days after first immunization with chicken CII.