Inducible costimulator is essential for collagen-induced arthritis.
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.
Nurieva
Roza I
RI
Department of Immunology, and. Department of Comparative Medicine, University of Washington School of Medicine, Seattle, Washington, USA.
Treuting
Piper
P
Duong
Julie
J
Flavell
Richard A
RA
Dong
Chen
C
D000818:Animals; D000917:Antibody Formation; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D001172:Arthritis, Rheumatoid / Q000209:etiology* / Q000473:pathology; D018106:CD28 Antigens / Q000502:physiology; D023201:CD40 Ligand / Q000032:analysis; D024043:Collagen Type II / Q000276:immunology*; D007114:Immunization; D060889:Inducible T-Cell Co-Stimulator Protein; D020381:Interleukin-17 / Q000096:biosynthesis; D051379:Mice; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000276:immunology
D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D024043:Collagen Type II; C556694:Icos protein, mouse; D060889:Inducible T-Cell Co-Stimulator Protein; D020381:Interleukin-17; D023201:CD40 Ligand