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

King's College London
Novo Nordisk A/S
University of Amsterdam

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

111 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

UN SDGs

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

SDG 3 Good Health and Well-being

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

Access to Document

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.\}",

year = "2014",

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doi = "10.1038/ncomms4199",

language = "English",

volume = "5",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

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TY - JOUR

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

U2 - 10.1038/ncomms4199

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

UN SDGs

Keywords

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Annual European Congress of rheumatology (EULAR 2020)

Cite this