title: B cells contribute to heterogeneity of IL-17 producing cells in rheumatoid arthritis and healthy controls.
abstract: Secretion of the proinflammatory cytokine Interleukin-17A (IL-17A) is the hallmark of a unique lineage of CD4 T cells designated Th17 cells, which may play a crucial role in the pathogenesis of rheumatoid arthritis (RA) and many autoimmune diseases. Recently, IL-17-producing cells other than T cells have been described, including diverse innate immune cells. Here, we show that the cellular sources of IL-17A in RA include a significant number of non-T cells. Multicolour fluorescence analysis of IL-17-expressing peripheral blood mononuclear cells (PBMC) revealed larger proportions of IL-17(+)CD3(-) non-T cells in RA patients than in healthy controls (constitutive, 13.6% vs. 8.4%, and after stimulation with PMA/ionomycin 17.4% vs. 7.9% p < 0.001 in both cases). The source of IL-17 included CD3(-)CD56(+) NK cells, CD3(-)CD14(+) myeloid cells as well as the expected CD3(+)CD4(+) Th17 cells and surprisingly a substantial number of CD3(-)CD19(+) B cells. The presence of IL-17A-expressing B cells was confirmed by specific PCR of peripheral MACS-sorted CD19(+) B cells, as well as by the analysis of different EBV-transformed B cell lines. Here we report for the first time that in addition to Th17 cells and different innate immune cells B cells also contribute to the IL-17A found in RA patients and healthy controls.
authors: Section for Transplantation Immunology and Immunohematology, Department II, Medical Clinic, University Hospital, Tuebingen, Germany ; Department of Anesthesiology and Intensive Care Medicine, University Hospital, Tuebingen, Germany.
authors: Paul Martin
authors: PM
authors: Schlegel
authors: Ingeborg
authors: I
authors: Steiert
authors: Ina
authors: I
authors: Kötter
authors: Claudia A
authors: CA
authors: Müller
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D020381:Interleukin-17 / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000276:immunology / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology
chemical_list: C508717:IL17A protein, human; D020381:Interleukin-17