TNF-alpha 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 Kirkham; Leonie S. Taams

doi:10.1038/ncomms4199

TNF-alpha 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 Kirkham, Leonie S. Taams^*

^*Corresponding author for this work

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

100 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
Article number	3199
Number of pages	12
Journal	Nature Communications
Volume	5
Issue number	1
Early online date	4 Feb 2014
DOIs	https://doi.org/10.1038/ncomms4199
Publication status	Published - 4 Feb 2014

Keywords

REGULATORY T-CELLS
PATHOGENIC T(H)17 CELLS
GROWTH-FACTOR-BETA
RHEUMATOID-ARTHRITIS
TH17 CELLS
GENE-EXPRESSION
IFN-GAMMA
ACTIVATED MONOCYTES
JOINT INFLAMMATION
BONE EROSION

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/ncomms4199

Annual European Congress of rheumatology (EULAR 2020)
Taams, L. (Invited speaker)
3 Jun 2020 → 6 Jun 2020
Activity: Participating in or organising an event › Participation in conference

Cite this

@article{9e377f6852054a87b566bb3c7a44828e,

title = "TNF-alpha 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. ",

keywords = "REGULATORY T-CELLS, PATHOGENIC T(H)17 CELLS, GROWTH-FACTOR-BETA, RHEUMATOID-ARTHRITIS, TH17 CELLS, GENE-EXPRESSION, IFN-GAMMA, ACTIVATED MONOCYTES, JOINT INFLAMMATION, BONE EROSION",

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 Bruce Kirkham and Taams, {Leonie S.}",

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doi = "10.1038/ncomms4199",

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T1 - TNF-alpha 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

AU - Taams, Leonie S.

PY - 2014/2/4

Y1 - 2014/2/4

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.

KW - REGULATORY T-CELLS

KW - PATHOGENIC T(H)17 CELLS

KW - GROWTH-FACTOR-BETA

KW - RHEUMATOID-ARTHRITIS

KW - TH17 CELLS

KW - GENE-EXPRESSION

KW - IFN-GAMMA

KW - ACTIVATED MONOCYTES

KW - JOINT INFLAMMATION

KW - BONE EROSION

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DO - 10.1038/ncomms4199

M3 - Article

SN - 2041-1723

VL - 5

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 3199

ER -

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

Abstract

Keywords

UN SDGs

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Annual European Congress of rheumatology (EULAR 2020)

Cite this