Inducible costimulator is essential for collagen-induced arthritis.

نویسندگان

  • Roza I Nurieva
  • Piper Treuting
  • Julie Duong
  • Richard A Flavell
  • Chen Dong
چکیده

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.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

T Cell Vaccination as a Tool in the Treatment of Collagen Induced Arthritis in Albino Rats

Background: The effectiveness of T cell vaccination has been demonstrated in a variety of animal models of both induced and spontaneous autoimmune diseases. Objective: The purpose of this study was to test the T cell vaccination protocol to treat and prevent collagen induced arthritis (CIA) in a rheumatoid arthritis model. Methods: CIA was induced by an intradermal injection of an artheritogen ...

متن کامل

IL-4 Can Inhibit IL-17 Production in Collagen Induced Arthritis

Background: IL-4 is a cytokine that induces differentiation of naive helper T cells into Th2 cells. Once activated by IL-4, Th2 cells subsequently produce additional IL-4. Objective: To examine the effect of IL-4 on IL-17 production and its effect in Collagen- Induced Arthritis (CIA) mice. Method: In this study, a chicken collagen-II-induced experimental arthritis (CIA) model was used in DBA/1 ...

متن کامل

OX40 signaling is involved in the autoactivation of CD4+CD28− T cells and contributes to the pathogenesis of autoimmune arthritis

BACKGROUND CD4+CD28- T cells exhibit autoreactive potential in autoimmune disorders, including rheumatoid arthritis (RA). It is not well known which costimulator functions as an alternative second signal in the activation of this subset after CD28 expression is downregulated. Tumor necrosis factor receptor superfamily member OX40 is a key costimulator in the activation of T cells. The aim of th...

متن کامل

The Effect of Human Recombinant Tumor Necrosis Factor Receptor-2 on Reducing Inflammatory of Collagen -Induced Arthritis in Balb/c Mice

Background: The tumor necrosis factor alpha (TNFα) is a cytokine that produced principally by monocyte/macrophages and T lymphocytes, respectively. TNFα is recognized as the primary mediator of immunity in inflammation reaction.  One important application of Tumor Necrosis Factor Receptor 2 (TNFR2) is for the treatment of autoimmune diseases like rheumatoid arthritis (RA).<br /...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • The Journal of clinical investigation

دوره 112 10  شماره 

صفحات  -

تاریخ انتشار 2003