%0 Journal Article
%T Activated ¦Â-catenin in Foxp3+ regulatory T cells links inflammatory environments to autoimmunity
%J -
%D 2018
%R https://doi.org/10.1038/s41590-018-0236-6
%X 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-¦Ã 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 ¦Â-catenin as a key regulator of IFN-¦Ã and IL-10 expression. The activated ¦Â-catenin signature was enriched in human IFN-¦Ã+ Treg cells, as confirmed in vivo with Treg-specific ¦Â-catenin-stabilized mice exhibiting lethal autoimmunity with a dysfunctional Treg phenotype. Moreover, we identified prostaglandin E receptor 2 (PTGER2) as a regulator of IFN-¦Ã and IL-10 production under a high-salt environment, with skewed activation of the ¦Â-catenin¨CSGK1¨CFoxo axis. Our findings reveal a novel PTGER2¨C¦Â-catenin loop in Treg cells linking environmental high-salt conditions to autoimmunity
%U https://www.nature.com/articles/s41590-018-0236-6