Prostaglandin I2 Signaling and Inhibition of Group 2 Innate Lymphoid Cell Responses

Rationale: Group 2 innate lymphoid cells (ILC2s) robustly produce IL-5 and IL-13, cytokines central to the asthma phenotype; however, the effect of prostaglandin (PG) I2 on ILC2 function is unknown.Objectives: To determine the effect of PGI2 on mouse and human ILC2 cytokine expression in vitro and the effect of endogenous PGI2 and the PGI2 analog cicaprost on lung ILC2s in vivo.Methods: Flow-sorted bone marrow ILC2s of wild-type (WT) and PGI2 receptor–deficient (IP−/−) mice were cultured with IL-33 and treated with the PGI2 analog cicaprost. WT and IP−/− mice were challenged intranasally with Alternaria alternata extract for 4 consecutive days to induce ILC2 responses, and these were quantified. Prior to A. alternata extract, challenged WT mice were treated with cicaprost. Human flow-sorted peripheral blood ILC2s were cultured with IL-33 and IL-2 and treated with the PGI2 analog cicaprost.Measurement and Main Results: We demonstrate that PGI2 inhibits IL-5 and IL-13 protein expression by IL-33–stimulated ...