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

Hayley G. Evans; Urmas Roostalu; Gina J. Walter; Nicola J. Gullick; Klaus S. Frederiksen; Ceri A. Roberts; Jonathan Sumner; Dominique L. Baeten; Jens G. Gerwien; Andrew P. Cope; Frederic Geissmann; Bruce W. Kirkham; Leonie S. Taams

doi:https://doi.org/10.1038/ncomms4199

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

Hayley G. Evans, Urmas Roostalu, Gina J. Walter, Nicola J. Gullick, Klaus S. Frederiksen, Ceri A. Roberts, Jonathan Sumner, Dominique L. Baeten, Jens G. Gerwien, Andrew P. Cope, Frederic Geissmann, Bruce W. Kirkham, Leonie S. Taams

Research output: Contribution to journal › Article › Academic › peer-review

92 Citations (Scopus)

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

Original language	English
Pages (from-to)	3199
Journal	Nature communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms4199
Publication status	Published - 2014

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https://doi.org/10.1038/ncomms4199

Cite this

@article{12699157601c4a3ba6098ed2b1560a45,

title = "TNF-α blockade induces IL-10 expression in human CD4+ T cells",

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",

author = "Evans, {Hayley G.} and Urmas Roostalu and Walter, {Gina J.} and Gullick, {Nicola J.} and Frederiksen, {Klaus S.} and Roberts, {Ceri A.} and Jonathan Sumner and Baeten, {Dominique L.} and Gerwien, {Jens G.} and Cope, {Andrew P.} and Frederic Geissmann and Kirkham, {Bruce W.} and Taams, {Leonie S.}",

year = "2014",

doi = "https://doi.org/10.1038/ncomms4199",

language = "English",

volume = "5",

pages = "3199",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - TNF-α blockade induces IL-10 expression in human CD4+ T cells

AU - Evans, Hayley G.

AU - Roostalu, Urmas

AU - Walter, Gina J.

AU - Gullick, Nicola J.

AU - Frederiksen, Klaus S.

AU - Roberts, Ceri A.

AU - Sumner, Jonathan

AU - Baeten, Dominique L.

AU - Gerwien, Jens G.

AU - Cope, Andrew P.

AU - Geissmann, Frederic

AU - Kirkham, Bruce W.

AU - Taams, Leonie S.

PY - 2014

Y1 - 2014

N2 - 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

AB - 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

U2 - https://doi.org/10.1038/ncomms4199

DO - https://doi.org/10.1038/ncomms4199

M3 - Article

C2 - 24492460

SN - 2041-1723

VL - 5

SP - 3199

JO - Nature communications

JF - Nature communications

ER -