title: Role of Th17 cells in human autoimmune arthritis.
abstract: OBJECTIVE
  To delineate the role of Th17 cells in the pathogenesis of autoimmune arthritides.
  
  
  METHODS
  Th17 cells were analyzed in well-defined homogeneous cohorts of patients with the prototypical autoimmune arthritides rheumatoid arthritis (RA) and psoriatic arthritis (PsA), grouped according to patients who had very early active RA (n = 36; mean disease duration 2.8 months, Disease Activity Score in 28 joints 5.0) and those who had very early active PsA (n = 20; mean disease duration 2.3 months), none of whom had received treatment with glucocorticoids or disease-modifying antirheumatic drugs, as well as patients with established RA (n = 21; mean disease duration 68 months) who were considered either responders or nonresponders to therapy. Groups of healthy individuals and patients with osteoarthritis (a noninflammatory arthritis) were used as control cohorts. Expression of T lineage-specific transcription factors (RORC, T-bet, GATA-3, and FoxP3) and the response of CD4 T cells to Th17 cell-inducing conditions were analyzed in vitro.
  
  
  RESULTS
  The frequencies of Th17 cells and levels of interleukin-17 strongly correlated with systemic disease activity at both the onset and the progression of RA or PsA. The values were reduced to control levels in patients with treatment-controlled disease activity. Th17 cells were enriched in the joints, and increased frequencies of synovial Th17 cells expressed CCR4 and CCR6, indicative of selective migration of Th17 cells to the joints. The intrinsically elevated expression of RORC, accompanied by biased Th17 cell development, and the resistance of Th17 cells to a natural cytokine antagonist in patients with RA and patients with PsA were suggestive of the underlying molecular mechanisms of uncontrolled Th17 activity in these patients.
  
  
  CONCLUSIONS
  Th17 cells play an important role in inflammation in human autoimmune arthritides, both at the onset and in established disease.
authors.affiliation: Medizinische Poliklinik and University of Munich, Munich, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Leipe
authors.forename: Mathias
authors.initials: M
authors.lastname: Grunke
authors.forename: Claudia
authors.initials: C
authors.lastname: Dechant
authors.forename: Christiane
authors.initials: C
authors.lastname: Reindl
authors.forename: Ulrike
authors.initials: U
authors.lastname: Kerzendorf
authors.forename: Hendrik
authors.initials: H
authors.lastname: Schulze-Koops
authors.forename: Alla
authors.initials: A
authors.lastname: Skapenko
mesh_terms: D000328:Adult; D000368:Aged; D015535:Arthritis, Psoriatic / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation / Q000276:immunology; D020381:Interleukin-17 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis; D010641:Phenotype; D012720:Severity of Illness Index; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: C508717:IL17A protein, human; D020381:Interleukin-17