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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

1
Centre for Molecular & Cellular Biology of Inflammation (CMCBI), Division of Immunology, Infection and Inflammatory Disease, King's College London, SE1 1UL, UK.
2
Novo Nordisk A/S, Biopharmaceuticals Research Unit, Inflammation Biology, 2760 Måløv, Denmark.
3
Division of Clinical Immunology and Rheumatology, Academic Medical Centre, Amsterdam, 1105 AZ, the Netherlands.
4
Academic Department of Rheumatology, SE1 1UL, King's College London, UK.
5
Department of Rheumatology, Guy's & St Thomas' NHS Trust, London, SE1 9RT, UK.
#
Contributed equally

Abstract

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.

PMID:
24492460
PMCID:
PMC3918582
DOI:
10.1038/ncomms4199
[Indexed for MEDLINE]
Free PMC Article

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