Prostaglandin E2 suppresses human group 2 innate lymphoid cell function

Jovana Maric, Avinash Ravindran, Luca Mazzurana, Åsa K. Björklund, Aline Van Acker, Anna Rao, Danielle Friberg, Sven-Erik Dahlén, Akos Heinemann, Viktoria Konya, Jenny Mjösberg

Group 2 innate lymphoid cells (ILC2) are involved in the initial phase of type 2 inflammation and can amplify allergic immune responses by orchestrating other type 2 immune cells. PGE2 is a bioactive lipid that plays protective roles in the lung, particularly during allergic inflammation. We set out to investigate how PGE2 regulates human ILC2 function. The effects of PGE2 on human ILC2 proliferation, intracellular cytokine and transcription factor expression were assessed by flow cytometry. Cytokine production was measured by ELISA and real-time quantitative PCR was performed to detect PGE2 receptor expression. PGE2 inhibited the expression of GATA3, as well as the production of type 2 cytokines, IL-5 and IL-13, from human tonsil and blood ILC2 in response to stimulation with a combination of IL-25, IL-33, TSLP and IL-2. Furthermore, PGE2 downregulated the expression of IL-2Rα (CD25). In line with that observation, PGE2 decreased ILC2 proliferation. These effects were mediated by the combined action of the EP2 and EP4 receptors, which were specifically expressed on ILC2. Our findings reveal that PGE2 limits ILC2 activation and propose that selective EP2 and EP4 receptor agonists might serve as promising therapeutic approach in treating allergic diseases by suppressing ILC2 function.