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

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...

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Autores principales: Evans, Hayley G., Roostalu, Urmas, Walter, Gina J., Gullick, Nicola J., Frederiksen, Klaus S., Roberts, Ceri A., Sumner, Jonathan, Baeten, Dominique L., Gerwien, Jens G., Cope, Andrew P., Geissmann, Frederic, Kirkham, Bruce W., Taams, Leonie S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3918582/
https://www.ncbi.nlm.nih.gov/pubmed/24492460
http://dx.doi.org/10.1038/ncomms4199
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author Evans, Hayley G.
Roostalu, Urmas
Walter, Gina J.
Gullick, Nicola J.
Frederiksen, Klaus S.
Roberts, Ceri A.
Sumner, Jonathan
Baeten, Dominique L.
Gerwien, Jens G.
Cope, Andrew P.
Geissmann, Frederic
Kirkham, Bruce W.
Taams, Leonie S.
author_facet Evans, Hayley G.
Roostalu, Urmas
Walter, Gina J.
Gullick, Nicola J.
Frederiksen, Klaus S.
Roberts, Ceri A.
Sumner, Jonathan
Baeten, Dominique L.
Gerwien, Jens G.
Cope, Andrew P.
Geissmann, Frederic
Kirkham, Bruce W.
Taams, Leonie S.
author_sort Evans, Hayley G.
collection PubMed
description 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 characterised 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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spelling pubmed-39185822014-08-04 TNF-α blockade induces IL-10 expression in human CD4+ T cells Evans, Hayley G. Roostalu, Urmas Walter, Gina J. Gullick, Nicola J. Frederiksen, Klaus S. Roberts, Ceri A. Sumner, Jonathan Baeten, Dominique L. Gerwien, Jens G. Cope, Andrew P. Geissmann, Frederic Kirkham, Bruce W. Taams, Leonie S. Nat Commun Article 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 characterised 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. 2014-02-04 /pmc/articles/PMC3918582/ /pubmed/24492460 http://dx.doi.org/10.1038/ncomms4199 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Evans, Hayley G.
Roostalu, Urmas
Walter, Gina J.
Gullick, Nicola J.
Frederiksen, Klaus S.
Roberts, Ceri A.
Sumner, Jonathan
Baeten, Dominique L.
Gerwien, Jens G.
Cope, Andrew P.
Geissmann, Frederic
Kirkham, Bruce W.
Taams, Leonie S.
TNF-α blockade induces IL-10 expression in human CD4+ T cells
title TNF-α blockade induces IL-10 expression in human CD4+ T cells
title_full TNF-α blockade induces IL-10 expression in human CD4+ T cells
title_fullStr TNF-α blockade induces IL-10 expression in human CD4+ T cells
title_full_unstemmed TNF-α blockade induces IL-10 expression in human CD4+ T cells
title_short TNF-α blockade induces IL-10 expression in human CD4+ T cells
title_sort tnf-α blockade induces il-10 expression in human cd4+ t cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3918582/
https://www.ncbi.nlm.nih.gov/pubmed/24492460
http://dx.doi.org/10.1038/ncomms4199
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