期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 46, 期 6, 页码 1404-1414出版社
WILEY
DOI: 10.1002/eji.201546241
关键词
Autoantibody formation; B cell; Germinal center; Interleukin 22 (IL-22); Rheumatoid arthritis
类别
资金
- Dutch Arthritis Foundation (Reumafonds) [DAA 0801043]
- Netherlands Organization for Scientific Research (Zon-MW Vidi grant) [917.10.377]
- Netherlands Organization for Scientific Research (Zon-MW Veni grant) [916.13.011]
- Human Frontier Science Program [RGP0006/2009]
- Association pour la Recherche sur le Cancer
Interleukin 22 (IL-22) expression is associated with increased joint destruction and disease progression in rheumatoid arthritis (RA). Although IL-22 is considered a proinflammatory 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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