Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Activated Th17 Cells Drive Rheumatoid Inflammation and Are Resistant to Inhibition by Natural Antagonists of Their Development.
Leipe2, Jan, Grunke2, Mathias, Dechant2, Claudia, Reindl2, Christiane, Schulze-Koops1, Hendrik, Skapenko2, Alla
IL-17 has been identified as a new pro-inflammatory cytokine contributing to autoimmune inflammation in several animal models. Since the major source of IL-17 in human autoimmune diseases is still elusive, we analyzed Th17 cells, defined as a cell type producing IL-17, but not IFN-g or IL-4, in patients with the prototypic autoimmune diseases, rheumatoid arthritis (RA) and psoriatic arthritis (PsA).
Th17 cells were analyzed ex vivo and in vitro by various methods e.g. multi-color flow cytometry, enzyme-linked immunosorbent assay (ELISA) and real-time PCR in well-defined cohorts of patients: active treatment-naive RA (n = 36) and PsA (n = 20) with very early disease (disease duration < 3 months), and patients with established RA (n = 21; mean disease duration 68 months) responding or not responding to therapy. For control, patients with osteoarthritis (n=20) and age-matched healthy individuals (n=25) were analyzed.
Summary of the Results:
Th17 cell frequencies and IL-17 production of CD4 T cells from the peripheral blood of RA and PsA patients were significantly increased compared to controls. Importantly, Th17 cells frequencies strongly correlated with systemic disease activity in early (r = 0.91, p < 0.0001) and established (r = 0.72, p < 0.001) RA, and were reduced to control levels in response to clinically effective treatment. Th17 cells were specifically enriched in the inflamed joints of RA and PsA patients, and increased frequencies of synovial Th17 cells expressed the chemokine receptors CCR4 and CCR6 required for selective migration of Th17 cells into the joints. As molecular mechanisms underlying the pathophysiological Th17 cell activity in autoimmune arthritis, we identified an intrinsically elevated expression of the master transcription factor for Th17 cells, RORC, accompanied by increased Th17 cell differentiation, and a resistance of Th17 cells from the RA and PsA patients to the natural antagonists of their development, e.g. IL-4 and IFN-g.
Together the data indicate an important role of Th17 cells and their effector functions in the pathogenesis of autoimmune arthritides and provide the scientific basis for treatment approaches targeting Th17 cell functions.
To cite this abstract, please use the following information:
Leipe, Jan, Grunke, Mathias, Dechant, Claudia, Reindl, Christiane, Schulze-Koops, Hendrik, Skapenko, Alla; Activated Th17 Cells Drive Rheumatoid Inflammation and Are Resistant to Inhibition by Natural Antagonists of Their Development. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :2130