Activated β-catenin in Foxp3+ regulatory T cells links inflammatory environments to autoimmunity.
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
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.
Date Issued
2018-10-29
Date Acceptance
2018-09-11
Citation
Nature Immunology, 2018, 19 (12), pp.1391-1402
ISSN
1529-2908
Publisher
Nature Publishing Group
Start Page
1391
End Page
1402
Journal / Book Title
Nature Immunology
Volume
19
Issue
12
Copyright Statement
© 2018 Springer Nature Limited. All rights reserved. The final publication is available at https://dx.doi.org/10.1038/s41590-018-0236-6
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/30374130
PII: 10.1038/s41590-018-0236-6
Subjects
1107 Immunology
Immunology
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2018-10-29