Retinoic acid determines the precise tissue tropism of inflammatory Th17 cells in the intestine.
Retinoic acid determines the precise tissue tropism of inflammatory Th17 cells in the intestine.
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DOI：
10.4049/jimmunol.0903942
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发表时间：
2010-05-15
期刊：
影响因子：
--
通讯作者：
Kim CH
中科院分区：
文献类型：
--
作者：
Wang C;Kang SG;HogenEsch H;Love PE;Kim CH
Th17细胞是肠道中的主要效应T细胞，但对其在肠道内的组织趋向性的调节知之甚少。在这里，我们研究了维生素A和维甲酸在肠道内具有不同组织趋向性的炎性Th17细胞产生中的作用。我们发现，具有不同组织趋向性和致病活性的Th17细胞的产生取决于维甲酸(RA)的有效浓度。与普遍认为RA会抑制Th17细胞的生成相反，我们在这里提供的证据表明，在肠道内具有特定组织取向的Th17细胞的生成实际上需要RA。外源性RA(~10 nM)诱导的Th17细胞迁移至小肠，并引起更严重的炎症。在维甲酸存在或不存在的情况下，Th17细胞表达不同的转运受体CCR9和α4β7。CCR9是Th17细胞向小肠迁移所必需的，α4β7是Th17细胞在整个肠道迁移所必需的。我们的结果发现维甲酸是调节肠道Th17细胞产生的主要信号，该细胞具有不同的迁移和炎症活动能力。结果还表明，Th17细胞的特异性肠道趋向性是由RA信号调节的运输受体的组合决定的。
Th17 cells are major effector T cells in the intestine but the regulation of their tissue tropism within the gut is poorly understood. We investigated here the roles of vitamin A and retinoic acid in generation of inflammatory Th17 cells with distinct tissue tropisms within the intestine. We found that Th17 cells with distinct tissue tropisms and pathogenic activities are generated depending on the available concentration of retinoic acid (RA). In contrast to the widespread perception that RA would suppress the generation of Th17 cells, we provide evidence here that RA is actually required for generation of Th17 cells with specific tissue tropisms within the gut. Th17 cells induced at suboptimal serum concentrations of RA migrated and induced moderate inflammation mainly in the large intestine, whereas the Th17 cells induced with optimal levels of exogenous RA (~10 nM) migrated to the small intestine and induced more severe inflammation. The Th17 cells, induced in the presence or absence of retinoic acid, differentially expressed the trafficking receptors CCR9 and α4β7. CCR9 is required for Th17 cell migration to the small intestine, whileα4β7 is required for the migration of Th17 cells throughout the whole intestine. Our results identified retinoic acid as a major signal that regulates the generation of gut Th17 cells with distinct capacities in migration and inflammatory activities. The results indicate also that specific gut tropism of Th17 cells is determined by the combination of trafficking receptors regulated by the RA signal.
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影响因子：
29.4
作者：
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通讯作者：
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