Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Impaired B Cell Immunity in IL-22 Knock-Out Mice in Collagen Induced Arthritis.

Corneth1,  Odilia, Mus2,  Anne-Marie, Asmawidjaja2,  Patrick, Kil2,  Laurens, Ouyang3,  Wenjun, Hendriks2,  Rudi, Lubberts2,  Erik

Erasmus MC, University Medical Center, Rotterdam, ZH, The Netherlands
Erasmus MC, University Medical Center
Genentech

Background:

The role of IL-22, a cytokine produced by Th17 cells, in autoimmunity is not fully understood. Previous research has shown that IL-22 is important in the development of collagen induced arthritis (CIA). However, the mechanism behind the apparent protection in IL-22 knock-out mice against CIA remains unclear.

Objective:

To investigate the mechanisms by which IL-22 knock-out mice are protected against collagen induced arthritis.

Materials and Methods:

For CIA, IL-22 knock-out and wild type mice were immunized with chicken collagen type II (CII) and complete Freud's adjuvant (CFA) and boosted 21 days later. Antigen specific serum IgG levels were measured by ELISA. Mice were sacrificed 50 days after immunization. Splenocytes were analyzed by flow cytometry and immunohistochemistry (IHC). Functional assays were performed with splenic Th17 cells sorted from mice ten days after immunization. For antigen induced arthritis (AIA), mice were immunized with methylated bovine serum albumin (mBSA) and CFA and triggered seven days later by intra-articular mBSA injection.

Results:

In IL-22 knock-out mice, the severity of CIA was lower compared to wild type controls. No significant difference in disease incidence was observed between wild type and IL-22 knock-out mice. This prompted us to study the pathogenicity of Th17 cells from these mice. Synovial fibroblasts produced higher levels of IL-6 when co-cultured with Th17 cells from IL-22 knock-out mice compared to wild type Th17 cells. To study the pathogenicity of these cells in vivo, we made use of the Th17 mediated AIA model. IL-22 knock-out mice developed AIA similarly to wild type controls, showing that Th17 cells function normally in vivo. As CIA is strongly driven by B cells and immune complexes, we investigated whether B cell immunity is normal in IL-22 knock-out mice. Antigen specific serum IgG2a levels were significantly lower in IL-22 knock-out mice at early onset of disease. Flow cytometric analysis of splenic B cells showed no significant differences in B cell numbers or activation. However, IHC slides of spleens from IL-22 knock-out mice show no or very small germinal centers and fewer IgG2a plasma cells compared to wild type controls.

Discussion:

Here we show that lack of IL-22 production affects B cell immunity in CIA. We show that Th17 cells in IL-22 knock-out mice function normally in vitro in a functional assay and in vivo in antigen induced arthritis (AIA). This indicates that the lack of IL-22 production does not affect the pathogenicity of Th17 cells. However, germinal center formation, plasma cell formation and IgG2a antibody production are lower in IL-22 knock-out mice in CIA, suggesting that IL-22 has a role in further differentiation of B cells in autoimmunity.

To cite this abstract, please use the following information:
Corneth, Odilia, Mus, Anne-Marie, Asmawidjaja, Patrick, Kil, Laurens, Ouyang, Wenjun, Hendriks, Rudi, et al; Impaired B Cell Immunity in IL-22 Knock-Out Mice in Collagen Induced Arthritis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :715
DOI: 10.1002/art.28483

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