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.

Autoantibody formation, B cell, Germinal center, Interleukin 22 (IL-22), Rheumatoid arthritis,
European Journal of Immunology
Erasmus MC: University Medical Center Rotterdam

Corneth, O.B.J, Reijmers, R.M, Mus, A.M.C, Asmawidjaja, P, van Hamburg, J.P, Papazian, N, … Lubberts, E.W. (2016). Loss of IL-22 inhibits autoantibody formation in collagen-induced arthritis in mice. European Journal of Immunology. doi:10.1002/eji.201546241