オクニシ　カツヒデ   Okunishi Katsuhide   奥西　勝秀    所属   東邦大学  医学部 医学科    職種   教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Prostaglandin E₂ suppresses allergic sensitization and lung inflammation by targeting the E prostanoid 2 receptor on T cells.
掲載誌名	正式名：The Journal of allergy and clinical immunology ISSNコード：0091-6749/1097-6825
掲載区分	国外
出版社	MOSBY-ELSEVIER
巻・号・頁	133(2),pp.379-87
著者・共著者	Zbigniew Zasłona,Katsuhide Okunishi,Emilie Bourdonnay,Racquel Domingo-Gonzalez,Bethany B Moore,Nicholas W Lukacs,David M Aronoff,Marc Peters-Golden
発行年月	2014/02
概要	BACKGROUND: Endogenous prostanoids have been suggested to modulate sensitization during experimental allergic asthma, but the specific role of prostaglandin (PG) E₂ or of specific E prostanoid (EP) receptors is not known. OBJECTIVE: Here we tested the role of EP2 signaling in allergic asthma. METHODS: Wild-type (WT) and EP2(-/-) mice were subjected to ovalbumin sensitization and acute airway challenge. The PGE2 analog misoprostol was administered during sensitization in both genotypes. In vitro culture of splenocytes and flow-sorted dendritic cells and T cells defined the mechanism by which EP2 exerted its protective effect. Adoptive transfer of WT and EP2(-/-) CD4 T cells was used to validate the importance of EP2 expression on T cells. RESULTS: Compared with WT mice, EP2(-/-) mice had exaggerated airway inflammation in this model. Splenocytes and lung lymph node cells from sensitized EP2(-/-) mice produced more IL-13 than did WT cells, suggesting increased sensitization. In WT but not EP2(-/-) mice, subcutaneous administration of misoprostol during sensitization inhibited allergic inflammation. PGE₂ decreased cytokine production and inhibited signal transducer and activator of transcription 6 phosphorylation by CD3/CD28-stimulated CD4(+) T cells. Coculture of flow cytometry-sorted splenic CD4(+) T cells and CD11c(+) dendritic cells from WT or EP2(-/-) mice suggested that the increased IL-13 production in EP2(-/-) mice was due to the lack of EP2 specifically on T cells. Adoptive transfer of CD4(+) EP2(-/-) T cells caused greater cytokine production in the lungs of WT mice than did transfer of WT CD4(+) T cells. CONCLUSION: We conclude that the PGE2-EP2 axis is an important endogenous brake on allergic airway inflammation and primarily targets T cells and that its agonism represents a potential novel therapeutic approach to asthma.
DOI	10.1016/j.jaci.2013.07.037
PMID	24075232