Prostaglandin E2 directly inhibits the conversion of inducible regulatory T cells through EP2 and EP4 receptors via antagonizing TGF-β signalling

Goepp, Marie, Crittenden, Siobhan, Zhou, You ORCID: https://orcid.org/0000-0002-1743-1291, Rossi, Adriano G, Narumiya, Shuh and Yao, Chengcan 2021. Prostaglandin E2 directly inhibits the conversion of inducible regulatory T cells through EP2 and EP4 receptors via antagonizing TGF-β signalling. Immunology 164 (4) , pp. 777-791. 10.1111/imm.13417

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Abstract

Regulatory T (Treg) cells are essential for control of inflammatory processes by suppressing effector T-cell functions. The actions of PGE2 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 PGE2 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 PGE2, which was mediated by the receptors EP2 and EP4. Mechanistically, PGE2-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 PGE2 negatively regulates iTreg cell differentiation through a direct action on T cells, highlighting the potential for selectively targeting the PGE2-EP2/EP4 pathway to control T cell-mediated inflammation.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Additional Information:	This is an open access article under the terms of the Creative Commons Attribution License
Publisher:	Wiley
ISSN:	0019-2805
Date of First Compliant Deposit:	7 October 2021
Date of Acceptance:	31 August 2021
Last Modified:	05 May 2023 10:14
URI:	https://orca.cardiff.ac.uk/id/eprint/144722

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