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 cellsdesignated Th17 cells, which may play a crucial role in the pathogenesis of rheumatoid arthritis (RA) and manyautoimmune diseases. Recently, IL-17-producing cells other than T cells have been described, including diverseinnate 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. © 2013 Schlegel et al.