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.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Evans HG,Roostalu U,Walter GJ,Gullick NJ,Frederiksen KS,Roberts CA,Sumner J,Baeten DL,Gerwien JG,Cope AP,Geissmann F,Kirkham BW,Taams LSdoi
10.1038/ncomms4199subject
Has Abstractpub_date
2014-01-01 00:00:00pages
3199issn
2041-1723journal_volume
5pub_type
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