Prostaglandin I2-IP signaling promotes Th1 differentiation in a mouse model of contact hypersensitivity.
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.
Nakajima
Saeko
S
Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Honda
Tetsuya
T
Sakata
Daiji
D
Egawa
Gyohei
G
Tanizaki
Hideaki
H
Otsuka
Atsushi
A
Moniaga
Catharina Sagita
CS
Watanabe
Takeshi
T
Miyachi
Yoshiki
Y
Narumiya
Shuh
S
Kabashima
Kenji
K
D019264:Adoptive Transfer; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D017449:Dermatitis, Allergic Contact / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D011464:Epoprostenol / Q000378:metabolism*; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D018078:Receptors, Prostaglandin E / Q000819:agonists / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D058306:Receptors, Prostaglandin E, EP1 Subtype; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics / Q000276:immunology
D047428:Protein Kinase Inhibitors; C545636:Ptger1 protein, mouse; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D011464:Epoprostenol; D017868:Cyclic AMP-Dependent Protein Kinases