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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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2014
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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. |
format | Online Article Text |
id | pubmed-3918582 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
record_format | MEDLINE/PubMed |
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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