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 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 that RA is actually required for generation of Th17 cells with specific tissue tropisms within the gut. Th17 cells inducedat suboptimal serumconcentrationsofRAmigratedandinducedmoderate inflammationmainly 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 RA, differentially expressed the trafficking receptors CCR9 and a4b7. CCR9 is required for Th17 cell migration to the small intestine, whereas a4b7 is required for the migration of Th17 cells throughout the whole intestine. Our results identified RAas 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 tropismof Th17 cells is determined by the combination of trafficking receptors regulated by the RA signal.
ASJC Scopus subject areas
- Immunology and Allergy