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THU0055 IL-21 Signaling in B Cells is Critical for the Development of Collagen Induced Arthritis in Mice
  1. K. Sakuraba1,2,
  2. K. Fujimura1,
  3. S. Kamura1,
  4. Y. Esaki1,
  5. H. Miyahara1,
  6. Y. Yoshikai2,
  7. H. Yamada2
  1. 1Clinical Reserch Center, National Hospital Organization Kyushu Medical Center
  2. 2Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan

Abstract

Background IL-21 is a T cell-derived cytokine whose receptor is expressed on variety of cells in immune system. IL-21was reported to be involved in the development of Th17 cells and follicular helper T cells, as well as in antibody production of B cells, all of which could be involved in the development of autoimmune diseases. Therefore, IL-21 might be involved in the pathogenesis of RA possibly via induction of pathogenic T cell responses and/or autoantibody production. However, these remains to be determined and might be analyzed in animal models of arthritis.

Objectives To clarify the roles of IL-21 signaling in the pathogenesis of autoimmune arthritis

Methods In order to declare the phathogenesis of IL-21 signaling for animal models of arthritis, we investigated the development of collagen-induced arthritis (CIA) in IL-21 receptor (IL-21R)-deficient mice. IL-21R-deificient or wild type (WT) C57BL/6 mice were immunized with chicken type II collagen (CII) emulsified in CFA on day 0 and were given boost injection with CII on day 21. Analyses of lymphcytes in regional lymph nodes by flow cytemeter and antigen (CII)-specific antibodys in serum were done. Lymphocytes of regional lymph nodes were restimurated by CII in vitro and then were analyzed by flow cytometer. Culture supernatants were also analyzed by ELISA. RAG-deficient mice which transfered T and B cells from WT or IL-21 R-deficient mice were induced CIA, because of comfirming which cells demand IL-21 signaling for developing arthritis in vivo.

Results We found that IL-21R-deficient mice were resistant to the development of CIA. CII-specific antibody production was severely impaired in IL-21R-deficitent mice, which is consistent with the reduction of germinal center B cells. On the other hand, development of Th17 and Tfh cells was largely unaffected by the absence of IL-21 signaling. In addition, RAG-deficient mice were transferred WT CD4 T cells with WT or IL-21R-deficient B cells, and soon were induced CIA. We found that RAG-deficient mice transferred IL-21R-deficient B cells were resistant to the development of CIA, although which transferred WT B cells were susceptible.

Conclusions Thus, IL-21 signaling is critically involved in the development of CIA mainly by inducing pathogenic autoantibody production of B cells.

References

  1. Korn T, et al. Nature. 2007 Jul 26;448(7152):484-7.

  2. Nuriva RI, et al. Immunity. 2008 Jul 18;29(1):138-49.

  3. Litterman MA, et al. J Exp Med. 2010 Feb 15;207(2):353-63.

  4. Zotos D, et al. J Exp Med. 2010 Feb 15;207(2):365-78.

Disclosure of Interest None declared

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