title: IL-17/Th17 mediated synovial inflammation is IL-22 independent.
abstract: BACKGROUND
  Interleukin (IL)-17A and Th17 cells are critically involved in T cell-mediated synovial inflammation. Besides IL-17A, Th17 cells produce IL-22. Recently, Th22 cells were discovered, which produce IL-22 in the absence of IL-17. However, it remains unclear whether IL-22 and Th22 cells contribute to T cell-mediated synovial inflammation. Therefore, we examined the potential of IL-22 and Th22 cells to induce synovial inflammation and whether IL-22 is required for T cell-mediated experimental arthritis.
  
  
  METHODS
  Peripheral and synovial Th17 and Th22 cells were identified and sorted from patients with rheumatoid arthritis (RA). Co-culture experiments of these primary T cell populations with RA synovial fibroblasts (RASF) were performed. The in vivo IL-22 contribution to synovial inflammation was investigated by inducing T cell-mediated arthritis in IL-22 deficient mice and wild-type mice.
  
  
  RESULTS
  Peripheral Th17 and Th22 cell populations were increased in patients with RA and present in RA synovial fluid. In T cell-RASF co-cultures, IL-22 in the presence of IL-17A had limited effects on IL-6, IL-8, matrix metalloproteinase-1 (MMP-1) and MMP-3 production. Furthermore, primary peripheral blood and synovial Th17 cells were more potent in the induction of these factors by RASF compared with Th22 cells. In line with this, similar synovial inflammation and disease severity was found between IL-22 deficient and wild-type mice in T cell-mediated experimental arthritis.
  
  
  CONCLUSIONS
  These findings show that IL-17A/Th17 cell-mediated synovial inflammation is independent of IL-22 and Th22 cells. This implies that targeting IL-17A/Th17 cells, rather than IL-22/Th22 cells, should be the focus for treatment of T cell-mediated synovial inflammation.
authors: Department of Rheumatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors: Jan Piet
authors: JP
authors: van Hamburg
authors: Odilia B J
authors: OB
authors: Corneth
authors: Sandra M J
authors: SM
authors: Paulissen
authors: Nadine
authors: N
authors: Davelaar
authors: Patrick S
authors: PS
authors: Asmawidjaja
authors: Adriana M C
authors: AM
authors: Mus
authors: Erik
authors: E
authors: Lubberts
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D018920:Coculture Techniques; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis / Q000276:immunology*; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis / Q000276:immunology*; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D054399:Receptors, CCR6 / Q000032:analysis; D013585:Synovitis / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology; D055815:Young Adult; D000097043:Interleukin-22
chemical_list: D020381:Interleukin-17; D015850:Interleukin-6; D016209:Interleukin-8; D007378:Interleukins; D020781:Matrix Metalloproteinase 1; D019278:Matrix Metalloproteinase 3; D054399:Receptors, CCR6; D000097043:Interleukin-22; C106311:CCR6 protein, human; C508717:IL17A protein, human
keywords: Cytokines; Inflammation; Rheumatoid Arthritis; Synovitis; T Cells