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 and Leonie S. Taams ()
Additional contact information
Hayley G. Evans: Centre for Molecular and Cellular Biology of Inflammation (CMCBI), Infection and Inflammatory Disease, King’s College London
Urmas Roostalu: Centre for Molecular and Cellular Biology of Inflammation (CMCBI), Infection and Inflammatory Disease, King’s College London
Gina J. Walter: Centre for Molecular and Cellular Biology of Inflammation (CMCBI), Infection and Inflammatory Disease, King’s College London
Nicola J. Gullick: Centre for Molecular and Cellular Biology of Inflammation (CMCBI), Infection and Inflammatory Disease, King’s College London
Klaus S. Frederiksen: Biopharmaceuticals Research Unit, Inflammation Biology, Novo Nordisk A/S
Ceri A. Roberts: Centre for Molecular and Cellular Biology of Inflammation (CMCBI), Infection and Inflammatory Disease, King’s College London
Jonathan Sumner: Centre for Molecular and Cellular Biology of Inflammation (CMCBI), Infection and Inflammatory Disease, King’s College London
Dominique L. Baeten: Academic Medical Centre/University of Amsterdam
Jens G. Gerwien: Biopharmaceuticals Research Unit, Inflammation Biology, Novo Nordisk A/S
Andrew P. Cope: Centre for Molecular and Cellular Biology of Inflammation (CMCBI), Infection and Inflammatory Disease, King’s College London
Frederic Geissmann: Centre for Molecular and Cellular Biology of Inflammation (CMCBI), Infection and Inflammatory Disease, King’s College London
Bruce W. Kirkham: Guy’s and St Thomas’ NHS Trust
Leonie S. Taams: Centre for Molecular and Cellular Biology of Inflammation (CMCBI), Infection and Inflammatory Disease, King’s College London

Nature Communications, 2014, vol. 5, issue 1, 1-12

Abstract: 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.

Date: 2014
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms4199 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4199

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms4199

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().