title: Loss of IL-22 inhibits autoantibody formation in collagen-induced arthritis in mice.
abstract: 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.
authors.affiliation: Department of Rheumatology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Odilia B J
authors.initials: OB
authors.lastname: Corneth
authors.affiliation: Department of Hematology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Rogier M
authors.initials: RM
authors.lastname: Reijmers
authors.affiliation: Department of Rheumatology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Adriana M C
authors.initials: AM
authors.lastname: Mus
authors.affiliation: Department of Rheumatology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Asmawidjaja
authors.affiliation: Department of Rheumatology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Jan Piet
authors.initials: JP
authors.lastname: van Hamburg
authors.affiliation: Department of Hematology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Natalie
authors.initials: N
authors.lastname: Papazian
authors.affiliation: Department of Hematology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Jurre Y
authors.initials: JY
authors.lastname: Siegers
authors.affiliation: INSERM U917, Rennes 1 University, EFS, Rennes, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Mourcin
authors.affiliation: INSERM U917, Rennes 1 University, EFS, Rennes, France.
authors.forename: Rada
authors.initials: R
authors.lastname: Amin
authors.affiliation: INSERM U917, Rennes 1 University, EFS, Rennes, France.
authors.forename: Karin
authors.initials: K
authors.lastname: Tarte
authors.affiliation: Department of Pulmonary Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Rudi W
authors.initials: RW
authors.lastname: Hendriks
authors.affiliation: Department of Hematology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Tom
authors.initials: T
authors.lastname: Cupedo
authors.affiliation: Department of Rheumatology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Erik
authors.initials: E
authors.lastname: Lubberts
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000235:genetics* / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology; D001169:Arthritis, Experimental / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001323:Autoantibodies / Q000276:immunology*; D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D018920:Coculture Techniques; D004195:Disease Models, Animal; D018858:Germinal Center / Q000276:immunology / Q000378:metabolism; D007378:Interleukins / Q000172:deficiency*; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism; D012720:Severity of Illness Index; D017154:Stromal Cells / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D001323:Autoantibodies; D018925:Chemokines; D007378:Interleukins; D018123:Receptors, Interleukin; D000097043:Interleukin-22; C415369:interleukin-22 receptor
keywords: Autoantibody formation; B cell; Germinal center; Interleukin 22 (IL-22); Rheumatoid arthritis