Imperial College London
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DrMargaritaDominguez-Villar

Faculty of Medicine, Department of Infectious Disease

Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 3735m.dominguez-villar Website

 
 
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Location

 

117Wright Fleming WingSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Sumida:2018:10.1038/s41590-018-0236-6,
author = {Sumida, T and Lincoln, MR and Ukeje, CM and Rodriguez, DM and Akazawa, H and Noda, T and Naito, AT and Komuro, I and Dominguez-Villar, M and Hafler, DA},
doi = {10.1038/s41590-018-0236-6},
journal = {Nature Immunology},
pages = {1391--1402},
title = {Activated β-catenin in Foxp3+ regulatory T cells links inflammatory environments to autoimmunity.},
url = {http://dx.doi.org/10.1038/s41590-018-0236-6},
volume = {19},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Foxp3+ regulatory T cells (Treg cells) are the central component of peripheral immune tolerance. Whereas a dysregulated Treg cytokine signature has been observed in autoimmune diseases, the regulatory mechanisms underlying pro- and anti-inflammatory cytokine production are elusive. Here, we identify an imbalance between the cytokines IFN-γ and IL-10 as a shared Treg signature present in patients with multiple sclerosis and under high-salt conditions. RNA-sequencing analysis on human Treg subpopulations revealed β-catenin as a key regulator of IFN-γ and IL-10 expression. The activated β-catenin signature was enriched in human IFN-γ+ Treg cells, as confirmed in vivo with Treg-specific β-catenin-stabilized mice exhibiting lethal autoimmunity with a dysfunctional Treg phenotype. Moreover, we identified prostaglandin E receptor 2 (PTGER2) as a regulator of IFN-γ and IL-10 production under a high-salt environment, with skewed activation of the β-catenin-SGK1-Foxo axis. Our findings reveal a novel PTGER2-β-catenin loop in Treg cells linking environmental high-salt conditions to autoimmunity.
AU  - Sumida,T
AU  - Lincoln,MR
AU  - Ukeje,CM
AU  - Rodriguez,DM
AU  - Akazawa,H
AU  - Noda,T
AU  - Naito,AT
AU  - Komuro,I
AU  - Dominguez-Villar,M
AU  - Hafler,DA
DO  - 10.1038/s41590-018-0236-6
EP  - 1402
PY  - 2018///
SN  - 1529-2908
SP  - 1391
TI  - Activated β-catenin in Foxp3+ regulatory T cells links inflammatory environments to autoimmunity.
T2  - Nature Immunology
UR  - http://dx.doi.org/10.1038/s41590-018-0236-6
UR  - https://www.ncbi.nlm.nih.gov/pubmed/30374130
UR  - http://hdl.handle.net/10044/1/64354
VL  - 19
ER  -
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