Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.

IL-27 Receptor Signaling Is Critical for B Cell Differentiation in Collagen Induced Arthritis.

Corneth1,  Odilia B.J., Mus2,  Anne-Marie, Asmawidjaja2,  Patrick S., Hendriks2,  Rudi W., Lubberts2,  Erik

Erasmus MC, University Medical Center, Rotterdam, Rotterdam, Netherlands
Erasmus MC, University Medical Center, Rotterdam, Netherlands


Th17 cells play a critical role in the autoimmune mouse model for rheumatoid arthritis, collagen induced arthritis (CIA). IL-27 receptor (IL-27R) signaling induces Th1 differentiation and IL-10 production and inhibits Th17 differentiation. In addition, IL-27R signaling is linked to B cell proliferation and IgG2a class switch recombination. In experimental autoimmune encephalomyelitis (EAE), an autoimmune mouse model for multiple sclerosis, IL-27R knock-out mice showed higher proliferation of draining lymph nodes with more production of IL-17, IL-6 and TNFa. We therefore hypothesized that CIA would be enhanced in IL-27R knock-out mice compared to wild type controls. The purpose of this study is to investigate the role of IL-27R signaling in CIA.


IL-27R knock-out mice and wild type controls were immunized with chicken collagen type II and complete Freunds Adjuvant (CFA), and boosted again 21 days later. Mice were euthanized 10, 36, 45 and 63 days after immunization and B and T cell subsets in spleen, lymph nodes and joints were analyzed using flow cytometry. Furthermore, auto-antibodies were determined in serum using ELISA and immunohistochemic analysis of the spleen and histological analysis of the joints was performed. For antigen induced arthritis, mice were immunized with methylated bovine serum albumin (mBSA) in CFA and a local injection of mBSA in the knee joint was given one week later.


Interestingly, both the incidence of CIA and the arthritis score were significantly lower in IL-27R knock-out mice compared to wild type controls. In addition, synovial inflammation was markedly decreased in IL-27R knock-out mice. Although the proportion of Th17 cells was increased in IL-27R knock-out mice, the total number of CD4+ T cells was significantly lower. To assess whether Th17 cells were pathogenic we made use of the Th17 mediated antigen induced arthritis (AIA) model. Inflammation of the knee joints in IL-27R knock-out mice in AIA was comparable to wild type controls, showing that the pathogenicity of these cells is normal. As B cells also play a significant role in CIA, we then analyzed B cells by flow cytometry. The total number of B cells was lower in IL-27R knock-out mice. Also, IL-27R knock-out mice hardly develop germinal center B cells, which we confirmed by immunohistochemistry. In line with this, we found that collagen specific IgG antibody levels were lower in these mice suggesting a critical role for IL-27R signaling in further differentiation of mature B cells.


Our data show a critical role of the IL-27 receptor signaling in the development of CIA. IL-27R deficient mice have a higher proportion of Th17 cells with normal pathogenic function but reduced numbers of CD4+ T cells en B cells. In addition, the development of germinal center B cells was significantly impaired. These data suggest that IL-27 receptor signaling is involved in both T en B cell development and function and that the lack of germinal center B cells in the IL-27R deficient mice is most critical for the reduced expression of CIA.

To cite this abstract, please use the following information:
Corneth, Odilia B.J., Mus, Anne-Marie, Asmawidjaja, Patrick S., Hendriks, Rudi W., Lubberts, Erik; IL-27 Receptor Signaling Is Critical for B Cell Differentiation in Collagen Induced Arthritis. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :2499

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