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Exosomes secreted from T cells have been shown to affect dendritic cells, cancer cells, and other T cells. However, little is known about how T-cell exosomes (T exosomes) modulate endothelial cell functions in the context of tissue-specific homing. Here, we study the roles of T exosomes in the regulation of gut-specific T-cell homing. The gut-tropic T cells induced by retinoic acid secrete the exosomes that upregulate integrin a4b7 binding to the MAdCAM-1 expressed on high endothelial venules in the gut. T exosomes were preferentially distributed to the villi of the small intestine in an a4b7-dependent manner. Exosomes from gut-tropic T cells suppressed the expression of MAdCAM-1 in the small intestine, thereby inhibiting T-cell homing to the gut. Moreover, microRNA (miRNA) profiling analysis has shown that exosomes from gut-tropic T cells were enriched with miRNAs targeting NKX2.3, a transcription factor critical to MAdCAM-1 expression. Taken together, our study proposes that a4b7-expressing T exosomes distribute themselves to the small intestine and modify the expression of microenvironmental tissues such that any subsequent lymphocyte homing is precluded. This may represent a novel mechanism by which excessive lymphocyte homing to the intestinal tissues is downsized.
本文/Department of Molecular Pathobiology and Cell Adhesion Biology,Mie University Graduate School of Medicine, Tsu, Japan
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DOIinfo:doi/10.1182/bloodadvances.2018024877
Collection (particular)国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文
Date Accepted (W3CDTF)2020-01-15T13:48:52+09:00
Data Provider (Database)国立国会図書館 : 国立国会図書館デジタルコレクション