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

Odilia B. J. Corneth (1) , Rogier M. Reijmers (1) , Adriana M. C. Mus (1) , Patrick S. Asmawidjaja (1) , Jan Piet Van Hamburg (1) , Natalie Papazian (1) , Jurre Y. Siegers (1) , Frédéric Mourcin (2, 3) , Rada Amin (2) , Karin Tarte (4, 2) , Rudi W. Hendriks (1) , Tom Cupedo (1) , Erik Lubberts (1)

1 Erasmus MC - Erasmus University Medical Center [Rotterdam]
2 MiCa - Microenvironnement et cancer
3 Etablissement Français du Sang Bretagne
4 Service d’immunologie, de thérapie cellulaire et d’hématopoïèse

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.

Mots clés: Autoantibody formation; B cell; germinal center; Interleukin 22 (IL-22); Rheumatoid Arthritis

Domaines: Immunologie; Rhumatologie et système ostéo-articulaire

Odilia B. J. Corneth, Rogier M. Reijmers, Adriana M. C. Mus, Patrick S. Asmawidjaja, Jan Piet Van Hamburg, et al.. Loss of IL-22 inhibits autoantibody formation in collagen-induced arthritis in mice. European Journal of Immunology, 2016, 46 (6), pp.1404-1414. ⟨10.1002/eji.201546241⟩. ⟨hal-01305475⟩