Prostaglandin I2-IP signaling promotes Th1 differentiation in a mouse model of contact hypersensitivity

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

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)5595-5603
Number of pages9
JournalJournal of Immunology
Volume184
Issue number10
DOIs
Publication statusPublished - May 15 2010

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Prostaglandins I
Contact Dermatitis
Epoprostenol
Prostaglandins
Cyclic AMP-Dependent Protein Kinases
Dendritic Cells
Skin
Lymph Nodes
Glycogen Synthase
Protein Kinase Inhibitors
T-Cell Antigen Receptor
Real-Time Polymerase Chain Reaction
T-Lymphocytes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Prostaglandin I2-IP signaling promotes Th1 differentiation in a mouse model of contact hypersensitivity. / Nakajima, Saeko; Honda, Tetsuya; Sakata, Daiji; Egawa, Gyohei; Tanizaki, Hideaki; Otsuka, Atsushi; Moniaga, Catharina Sagita; Watanabe, Takeshi; Miyachi, Yoshiki; Narumiya, Shuh; Kabashima, Kenji.

In: Journal of Immunology, Vol. 184, No. 10, 15.05.2010, p. 5595-5603.

Research output: Contribution to journalArticle

Nakajima, S, Honda, T, Sakata, D, Egawa, G, Tanizaki, H, Otsuka, A, Moniaga, CS, Watanabe, T, Miyachi, Y, Narumiya, S & Kabashima, K 2010, 'Prostaglandin I2-IP signaling promotes Th1 differentiation in a mouse model of contact hypersensitivity', Journal of Immunology, vol. 184, no. 10, pp. 5595-5603. https://doi.org/10.4049/jimmunol.0903260
Nakajima, Saeko ; Honda, Tetsuya ; Sakata, Daiji ; Egawa, Gyohei ; Tanizaki, Hideaki ; Otsuka, Atsushi ; Moniaga, Catharina Sagita ; Watanabe, Takeshi ; Miyachi, Yoshiki ; Narumiya, Shuh ; Kabashima, Kenji. / Prostaglandin I2-IP signaling promotes Th1 differentiation in a mouse model of contact hypersensitivity. In: Journal of Immunology. 2010 ; Vol. 184, No. 10. pp. 5595-5603.
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