[HTML][HTML] TNF-α blockade induces IL-10 expression in human CD4+ T cells

HG Evans, U Roostalu, GJ Walter, NJ Gullick… - Nature …, 2014 - nature.com
HG Evans, U Roostalu, GJ Walter, NJ Gullick, KS Frederiksen, CA Roberts, J Sumner…
Nature communications, 2014nature.com
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 …
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.
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