Increased numbers of circulating polyfunctional Th17 memory cells in patients with seronegative spondylarthritides.
OBJECTIVE
A distinct subset of proinflammatory CD4+ T cells that produce interleukin-17 was recently identified. These cells are implicated in different autoimmune disease models, such as experimental autoimmune encephalomyelitis and collagen-induced arthritis, but their involvement in human autoimmune disease has not yet been clearly established. The purpose of this study was to assess the frequency and functional properties of Th17 cells in healthy donors and in patients with different autoimmune diseases.


METHODS
Peripheral blood was obtained from 10 psoriatic arthritis (PsA), 10 ankylosing spondylitis (AS), 10 rheumatoid arthritis (RA), and 5 vitiligo patients, as well as from 25 healthy donors. Synovial tissue samples from a separate group of patients were also evaluated (obtained as paraffin-embedded sections). Peripheral blood cells were analyzed by multiparameter flow cytometry and immunohistochemistry. Cytokine production was examined by enzyme-linked immunosorbent assay and intracellular cytokine staining using specific monoclonal antibodies. Synovial tissue was examined for infiltrating T cells by immunohistochemical analysis.


RESULTS
We found increased numbers of circulating Th17 cells in the peripheral blood of patients with seronegative spondylarthritides (PsA and AS), but not in patients with RA or vitiligo. In addition, Th17 cells from the spondylarthritis patients showed advanced differentiation and were polyfunctional in terms of T cell receptor-driven cytokine production.


CONCLUSIONS
These observations suggest a role of Th17 cells in the pathogenesis of certain human autoimmune disorders, in particular the seronegative spondylarthritides.
Jandus
Camilla
C
Ludwig Institute for Cancer Research, University Hospital (CHUV), Lausanne, Switzerland.
Bioley
Gilles
G
Rivals
Jean-Paul
JP
Dudler
Jean
J
Speiser
Daniel
D
Romero
Pedro
P
D015535:Arthritis, Psoriatic / Q000097:blood / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000473:pathology*; D016022:Case-Control Studies; D002454:Cell Differentiation; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology; D054399:Receptors, CCR6 / Q000378:metabolism; D025241:Spondylarthritis / Q000097:blood* / Q000276:immunology; D013167:Spondylitis, Ankylosing / Q000097:blood / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000378:metabolism* / Q000473:pathology*; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism / Q000473:pathology; D014820:Vitiligo / Q000097:blood
C106311:CCR6 protein, human; D020381:Interleukin-17; D054399:Receptors, CCR6