Prostaglandin I2-IP Signaling Promotes Th1 Differentiation in a Mouse Model of Contact Hypersensitivity
Prostaglandin I2-IP Signaling Promotes Th1 Differentiation in a Mouse Model of Contact Hypersensitivity
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DOI：
10.4049/jimmunol.0903260
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发表时间：
2010-05-15
影响因子：
4.4
通讯作者：
Kabashima, Kenji
中科院分区：
文献类型：
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作者：
Nakajima, Saeko;Honda, Tetsuya;Kabashima, Kenji
PGI(2)通过其特异性gs偶联I前列腺素受体（IP）发挥作用，已知存在于淋巴结中，但其在获得性皮肤免疫反应中的作用尚不清楚。为了研究PGI(2) IP信号在皮肤免疫反应中的作用，我们将IP缺陷（Ptgir(-/-)）小鼠作为获得性免疫反应模型，发现Ptgir（-/-）小鼠表现出明显降低的接触超敏反应。与对照小鼠相比，致敏Ptgir（-/-）小鼠的淋巴结细胞显示ifn - γ产生减少，T-bet（+）亚群较小。通过实时荧光定量PCR检测树突状细胞和T细胞中PGI合成酶和IP的表达，提示树突状细胞产生的PGI(2)作用于T细胞中的IP。事实上，在体外，Th1分化被IP激动剂增强，而这种增强被蛋白激酶A抑制剂抵消。这些结果表明，PGI(2) IP信号通过camp -蛋白激酶a途径促进Th1分化，从而启动获得性皮肤免疫反应。中华免疫学杂志，2010,18(4):595-5603。
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. The Journal of Immunology, 2010, 184: 5595-5603.