Details

Autor(en) / Beteiligte

• Yang, Yujian H.
• Istomine, Roman
• Alvarez, Fernando
• Al-Aubodah, Tho-Alfakar
• Shi, Xiang Qun
• Takano, Tomoko
• Thornton, Angela M.
• Shevach, Ethan M.
• Zhang, Ji
• Piccirillo, Ciriaco A.

Titel

Salt Sensing by Serum/Glucocorticoid-Regulated Kinase 1 Promotes Th17-like Inflammatory Adaptation of Foxp3+ Regulatory T Cells

Ist Teil von

• Cell reports (Cambridge), 2020-02, Vol.30 (5), p.1515-1529.e4

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• Regulatory T (Treg) cells integrate diverse environmental signals to modulate their function for optimal suppression. Translational regulation represents a favorable mechanism for Treg cell environmental sensing and adaptation. In this study, we carry out an unbiased screen of the Treg cell translatome and identify serum/glucocorticoid-regulated kinase 1 (SGK1), a known salt sensor in T cells, as being preferentially translated in activated Treg cells. We show that high salt (HS) drives thymic Treg cells to adopt a T helper type 17 (Th17)-like phenotype and enhances generation of Th17-like induced Treg cells in a SGK1-dependent manner, all the while maintaining suppressive function. Salt-mediated Th17-like differentiation of Treg cells was evident in mice fed with HS diet or injected with HS-preconditioned T cells. Overall, SGK1 enables Treg cells to adapt their function in response to environmental cues. By understanding these environmental-sensing mechanisms, we envision targeted approaches to fine-tune Treg cell function for better control of inflammation. [Display omitted] •The mRNA encoding salt-sensing SGK1 is preferentially translated in Foxp3+ Treg cells•HS promotes Th17-like adaptation in both tTreg and iTreg cell subsets via SGK1•HS-induced RORγt+ Treg cells are functionally adapted and suppressive•Helios− Treg cells are more susceptible than Helios+ Treg cells to the effects of salt Yang et al. demonstrate that high salt promotes Th17-like functional adaptation of both thymic and induced Foxp3+ Treg cell subsets through a salt-sensor protein, SGK1. The translationally regulated SGK1 pathway enables Treg cells to fine-tune their effector function in response to environmental cues during the dynamic course of inflammation.