Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Th17 but Not Th22 Cells Display Pathological Behaviour in Rheumatoid Arthritis Synovial Inflammation.
van Hamburg, Jan Piet, Corneth, Odilia B.J., Paulissen, Sandra M.J., Davelaar, Nadine, Asmawidjaja, Patrick S., Lubberts, Erik
T cells and their cytokines play a central role in the processes underlying synovial inflammation in rheumatoid arthritis (RA). In particular the IL-17A and IL-22 producing Th17 cells have been shown to be critically involved in the induction and progression of arthritis. Recently a novel Th22 subset was discovered, which was characterized by the expression of IL-22 in the absence of IL-17. However, it remains unclear whether Th22 cells, like Th17 cells, directly contribute to RA synovial inflammation. In this study we examined the potency of Th22 cells to activate synovial fibroblasts. In addition, it was investigated whether IL-22 is critical in Th17-mediated experimental arthritis.
Th17 (CD4+CD25-CCR6+CCR4+CCR10-) and Th22 (CD4+CD25-CCR6+CCR4+CCR10-) cells were analyzed in peripheral blood of treatment-naïve RA patients in comparison to age and sex matched healthy controls by flow cytometry. Furthermore, synovial fluid of patients with established RA was analysed for the presence of Th17 and Th22 cells. To test the contribution of IL-22 or Th22 in synovial inflammation, co-culture experiments of RA synovial fibroblasts (RASF) with Th22 and Th17 cells were performed. The in vivo relevance of IL-22 in synovial inflammation was investigated in a T cell-mediated arthritis model using mice deficient for IL-22.
Both the Th17 and Th22 cell populations were increased in peripheral blood of treatment naïve patients with early RA compared to age and sex matched healthy controls. In addition, Th17 and Th22 cells were present in synovial fluid of patients with early RA. When RASF were co-cultured with Th17 or Th22 cells, in both conditions the neutralisation of IL-22 resulted in an induction of the pro-inflammatory cytokine IL-6. In contrast, IL-22 activation with FICZ (6-formylindolo(3,2-b)carbazole) resulted in a reduction of IL-6. Comparing the RASF co-culture condition of Th17 with Th22, Th17 cells were markedly more potent than Th22 cells in the induction of IL-6, IL-8 and matrix metalloprotease (MMP)-1 and MMP-3. In line with this, mouse Th17 cells lacking IL-22 expression were able to induce IL-6 expression in mouse synovial fibroblasts similar as normal mouse Th17 cells. In addition, no difference in T cell-mediated experimental arthritis severity was found between IL-22 deficient mice compared to wild type mice.
These findings show that both Th17 and Th22 cells are present in patients with RA. However, in contrast to Th17 cells, Th22 cells are less potent activators of RASF activation and IL-22 even appear to have an inhibitory effect on IL-6 production. These data imply that treatment of T cell-mediated inflammatory arthritis should focus on targeting Th17 cells rather than Th22 cells.
To cite this abstract, please use the following information:
van Hamburg, Jan Piet, Corneth, Odilia B.J., Paulissen, Sandra M.J., Davelaar, Nadine, Asmawidjaja, Patrick S., Lubberts, Erik; Th17 but Not Th22 Cells Display Pathological Behaviour in Rheumatoid Arthritis Synovial Inflammation. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :2357