Prostaglandin I2–IP Signaling Promotes Th1 Differentiation in a Mouse Model of Contact Hypersensitivity

Abstract

PGI2, which exerts its actions via its specific Gs-coupled I prostanoid receptor (IP), is known to be present in the lymph nodes, but its roles in acquired cutaneous immune responses remain unclear. To investigate the role of PGI2–IP signaling in cutaneous immune responses, we applied IP-deficient (Ptgir−/−) mice to contact hypersensitivity as a model of acquired immune response and found that Ptgir−/− mice exhibited a significantly decreased contact hypersensitivity response. Lymph node cells from sensitized Ptgir−/− mice exhibited decreased IFN-γ production and a smaller T-bet+ subset compared with control mice. PGI synthase and IP expression were detected in dendritic cells and T cells, respectively, by quantitative real-time PCR analysis, suggesting that PGI2 produced by dendritic cells acts on IP in T cells. In fact, in vitro Th1 differentiation was enhanced by an IP agonist, and this enhancement was nullified by protein kinase A inhibitor. These results suggest that PGI2–IP signaling promotes Th1 differentiation through a cAMP-protein kinase A pathway and thereby initiates acquired cutaneous immune responses.