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

• Published in: European journal of immunology 2016-06, Vol.46 (6), p.1404-1414
• Main Authors: Corneth, Odilia B. J., Reijmers, Rogier M., Mus, Adriana M.C., Asmawidjaja, Patrick S., Hamburg, Jan Piet, Papazian, Natalie, Siegers, Jurre Y., Mourcin, Frédéric, Amin, Rada, Tarte, Karin, Hendriks, Rudi W., Cupedo, Tom, Lubberts, Erik
• Format: Article
• Language: English
• Subjects: Animals; Antibody Formation - genetics; Antibody Formation - immunology; Antibody Specificity - immunology; Arthritis; Arthritis, Experimental - etiology; Arthritis, Experimental - metabolism; Arthritis, Experimental - pathology; Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - metabolism; Arthritis, Rheumatoid - pathology; Autoantibodies - immunology; Autoantibody formation; B cell; Cells, Cultured; Chemokines - genetics; Chemokines - metabolism; Coculture Techniques; Disease Models, Animal; Germinal center; Germinal Center - immunology; Germinal Center - metabolism; Human health and pathology; Immunology; Interleukin 22 (IL‐22); Interleukin-22; Interleukins - deficiency; Life Sciences; Lymphocyte Activation; Mice; Mice, Knockout; Plasma Cells - immunology; Plasma Cells - metabolism; Receptors, Interleukin - genetics; Receptors, Interleukin - metabolism; Rheumatoid arthritis; Rhumatology and musculoskeletal system; Rodents; Severity of Illness Index; Stromal Cells - metabolism; Th17 Cells - immunology; Th17 Cells - metabolism
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201546241

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. (1) T cell‐derived IL‐22 activates lymphoid stroma through IL‐22R (2), which induces expression of germinal center (GC) dark zone CXCL12 and GC light zone CXCL13 (3). This facilitates the GC reaction, leading to autoantibody production by plasma cells (4).