Prostaglandin I 2 (PGI 2), a lipid mediator currently used in treatment of human disease, is a critical regulator of adaptive immune responses. Although PGI 2 signaling suppressed Th1 and Th2 immune responses, the role of PGI 2 in Th17 differentiation is not known.
In mouse CD4 +CD62L + naïve T cell culture, the PGI 2 analogs iloprost and cicaprost increased IL-17A and IL-22 protein production and Th17 differentiation in vitro. This effect was augmented by IL-23 and was dependent on PGI 2 receptor IP signaling. In mouse bone marrow-derived CD11c + dendritic cells (BMDCs), PGI 2 analogs increased the ratio of IL-23/IL-12, which is correlated with increased ability of BMDCs to stimulate naïve T cells for IL-17A production. Moreover, IP knockout mice had delayed onset of a Th17-associated neurological disease, experimental autoimmune encephalomyelitis (EAE), and reduced infiltration of IL-17A-expressing mononuclear cells in the spinal cords compared to wild type mice. These results suggest that PGI 2 promotes in vivo Th17 responses.