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Nat Commun. 2014;5:3199. doi: 10.1038/ncomms4199.

TNF-α blockade induces IL-10 expression in human CD4+ T cells.

Author information

Centre for Molecular & Cellular Biology of Inflammation (CMCBI), Division of Immunology, Infection and Inflammatory Disease, King's College London, SE1 1UL, UK.
Novo Nordisk A/S, Biopharmaceuticals Research Unit, Inflammation Biology, 2760 Måløv, Denmark.
Division of Clinical Immunology and Rheumatology, Academic Medical Centre, Amsterdam, 1105 AZ, the Netherlands.
Academic Department of Rheumatology, SE1 1UL, King's College London, UK.
Department of Rheumatology, Guy's & St Thomas' NHS Trust, London, SE1 9RT, UK.
Contributed equally


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.

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