Retinoic Acid Determines the Precise Tissue Tropism of Inflammatory Th17 Cells in the Intestine
Year: 2010
Type: article
Abstract: 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 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 (approximately 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 alpha4beta7. CCR9 is required for Th17 cell migration to the small intestine, whereas alpha4beta7 is required for the migration of Th17 cells throughout the whole intestine. Our results identified RA 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.
Source: The Journal of Immunology
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
Funders: Crohn's and Colitis Foundation of America, Purdue University, Crohn's and Colitis Foundation, National Institutes of Health, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1667031398, Genes and signals controlling mammalian hematopoiesis., Organ-specific migration of CD4+CD25+ regulatory T cells, Migration and function of Th17 cells in the gut, FoxP3+ T cells of mucosal tissues, Migration and function of Th17 cells in the gut, Therapeutic delivery of FoxP3+ T cells to the intestine, Genes and signals controlling mammalian hematopoiesis.
OpenAlex ID: W2149081932