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IL-17+ CD4+ T (Th17) cells contribute to the pathogenesis of several human inflammatory diseases. Here we demonstrate that TNF inhibitor (TNFi) drugs induce the anti-inflammatory cytokine IL-10 in CD4+ T cells including IL-17+ CD4+ T cells. TNFi-mediated induction of IL-10 in IL-17+ CD4+ T cells is Treg-/Foxp3-independent, requires IL-10 and is overcome by IL-1β. TNFi-exposed IL-17+ CD4+ T cells are molecularly and functionally distinct, with a unique gene signature characterized by expression of IL10 and IKZF3 (encoding Aiolos). We show that Aiolos binds conserved regions in the IL10 locus in IL-17+ CD4+ T cells. Furthermore, IKZF3 and IL10 expression levels correlate in primary CD4+ T cells and Aiolos overexpression is sufficient to drive IL10 in these cells. Our data demonstrate that TNF-α blockade induces IL-10 in CD4+ T cells including Th17 cells and suggest a role for the transcription factor Aiolos in the regulation of IL-10 in CD4+ T cells.

Original publication

DOI

10.1038/ncomms4199

Type

Journal article

Journal

Nat commun

Publication Date

2014

Volume

5

Keywords

Animals, Antirheumatic Agents, Arthritis, Rheumatoid, Base Sequence, Case-Control Studies, Cattle, Cells, Cultured, Conserved Sequence, Dogs, Humans, Ikaros Transcription Factor, Interleukin-10, Interleukin-1beta, Mice, Molecular Sequence Data, Rats, Sequence Homology, Nucleic Acid, Th17 Cells, Tumor Necrosis Factor-alpha