Differentiation and homeostasis of effector Treg cells are regulated by inositol polyphosphates modulating Ca²⁺ influx.

ABSTRACT: Activated Foxp3⁺ regulatory T (Treg) cells differentiate into effector Treg (eTreg) cells to maintain peripheral immune homeostasis and tolerance. T cell receptor (TCR)-mediated induction and regulation of store-operated Ca²⁺ entry (SOCE) is essential for eTreg cell differentiation and function. However, SOCE regulation in Treg cells remains unclear. Here, we show that inositol polyphosphate multikinase (IPMK), which generates inositol tetrakisphosphate and inositol pentakisphosphate, is a pivotal regulator of Treg cell differentiation downstream of TCR signaling. IPMK is highly expressed in TCR-stimulated Treg cells and promotes a TCR-induced Treg cell program. IPMK-deficient Treg cells display aberrant T cell activation and impaired differentiation into RORγt^+<

SUBMITTER: Min H 

PROVIDER: S-EPMC9271192 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature