| First Author | Sumida T | Year | 2018 |
| Journal | Nat Immunol | Volume | 19 |
| Issue | 12 | Pages | 1391-1402 |
| PubMed ID | 30374130 | Mgi Jnum | J:282537 |
| Mgi Id | MGI:6381222 | Doi | 10.1038/s41590-018-0236-6 |
| Citation | Sumida T, et al. (2018) Activated beta-catenin in Foxp3(+) regulatory T cells links inflammatory environments to autoimmunity. Nat Immunol 19(12):1391-1402 |
| abstractText | 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-gamma 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 beta-catenin as a key regulator of IFN-gamma and IL-10 expression. The activated beta-catenin signature was enriched in human IFN-gamma(+) Treg cells, as confirmed in vivo with Treg-specific beta-catenin-stabilized mice exhibiting lethal autoimmunity with a dysfunctional Treg phenotype. Moreover, we identified prostaglandin E receptor 2 (PTGER2) as a regulator of IFN-gamma and IL-10 production under a high-salt environment, with skewed activation of the beta-catenin-SGK1-Foxo axis. Our findings reveal a novel PTGER2-beta-catenin loop in Treg cells linking environmental high-salt conditions to autoimmunity. |
