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

2010; American Association of Immunologists; Volume: 184; Issue: 10 Linguagem: Inglês

10.4049/jimmunol.0903260

1550-6606

Saeko Nakajima, Tetsuya Honda, Daiji Sakata, Gyohei Egawa, Hideaki Tanizaki, Atsushi Otsuka, Catharina Sagita Moniaga, Takeshi Watanabe, Yoshiki Miyachi, Shuh Narumiya, Kenji Kabashima,

Drug-Induced Adverse Reactions

PGI(2), 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 PGI(2)-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-gamma 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 PGI(2) 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 PGI(2)-IP signaling promotes Th1 differentiation through a cAMP-protein kinase A pathway and thereby initiates acquired cutaneous immune responses.