Loss of IL-22 inhibits autoantibody formation in collagen-induced arthritis in mice

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Corneth, Odilia B. J. | Reijmers, Rogier M. | Mus, Adriana M. C. | Asmawidjaja, Patrick S. | Hamburg, Jan Piet, Van | Papazian, Natalie | Siegers, Jurre Y. | Mourcin, Frédéric | Amin, Rada | Tarte, Karin | Hendriks, Rudi W. | Cupedo, Tom | Lubberts, Erik

Edité par CCSD ; Wiley-VCH Verlag -

International audience. Interleukin 22 (IL-22) expression is associated with increased joint destruction and disease progression in rheumatoid arthritis (RA). Although IL-22 is considered a pro-inflammatory cytokine, its mechanism of action in RA remains incompletely understood. Here, we used the collagen-induced arthritis model in IL-22 deficient (IL-22(-/-) ) mice to study the role of IL-22 in RA. In spite of normal disease incidence, disease severity is significantly diminished in IL-22(-/-) mice. Moreover, pathogenicity of Th17 cells and development and function of B cells are unaffected. In contrast, splenic plasma cells, as well as serum autoantibody titers, are reduced in the absence of IL-22. At the peak of disease, germinal centers (GCs) are severely reduced in the spleens of IL-22(-/-) mice, correlating with a decline in GC B-cell numbers. Within the GC, we identified IL-22R1 expressing follicular dendritic cell-like stromal cells. Human lymphoid stromal cells respond to IL-22 ex vivo by inducing transcription of CXCL12 and CXCL13. We therefore postulate IL-22 as an important enhancer of the GC reaction, maintaining chemokine levels for the persistence of GC reactions, essential for the production of autoantibody-secreting plasma cells. Blocking IL-22 might therefore prevent immune-complex deposition and destruction of joints in RA patients.

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