Prostaglandin E ₂ directly inhibits the conversion of inducible regulatory T cells through EP2 and EP4 receptors via antagonizing TGF‐β signalling

Abstract

Abstract Regulatory T (Treg) cells are essential for control of inflammatory processes by suppressing effector T‐cell functions. The actions of PGE 2 on the development and function of Treg cells, particularly under inflammatory conditions, are debated. In this study, we employed pharmacological and genetic approaches to examine whether PGE 2 had a direct action on T cells to modulate de novo differentiation of Treg cells. We found that TGF‐β‐induced Foxp3 expression and iTreg cell differentiation in vitro is markedly inhibited by PGE 2 , which was mediated by the receptors EP2 and EP4. Mechanistically, PGE 2 ‐EP2/EP4 signalling interrupts TGF‐β signalling during iTreg differentiation. Moreover, EP4 deficiency in T cells impaired iTreg cell differentiation in vivo. Thus, our results demonstrate that PGE 2 negatively regulates iTreg cell differentiation through a direct action on T cells, highlighting the potential for selectively targeting the PGE 2 ‐EP2/EP4 pathway to control T cell‐mediated inflammation.