Exosomal regulation of lymphocyte homing to the gut
Exosomal regulation of lymphocyte homing to the gut
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DOI：
10.1182/bloodadvances.2018024877
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发表时间：
2019-01-08
期刊：
影响因子：
7.5
通讯作者：
Shimaoka, Motomu
中科院分区：
文献类型：
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作者：
Park, Eun Jeong;Prajuabjinda, Onmanee;Shimaoka, Motomu
T 细胞分泌的外泌体已被证明可以影响树突状细胞、癌细胞和其他 T 细胞。然而，人们对 T 细胞外泌体 (T exosomes) 如何在组织特异性归巢的情况下调节内皮细胞功能知之甚少。在这里，我们研究了 T 外泌体在调节肠道特异性 T 细胞归巢中的作用。视黄酸诱导的亲肠 T 细胞分泌外泌体，上调整合素 α 4 β 7 与肠道高内皮微静脉上表达的 MAdCAM-1 的结合。 T外泌体以α4β7依赖性方式优先分布到小肠绒毛。来自亲肠 T 细胞的外泌体抑制小肠中 MAdCAM-1 的表达，从而抑制 T 细胞归巢至肠道。此外，microRNA (miRNA) 分析表明，来自肠嗜性 T 细胞的外泌体富含针对 NKX2.3 的 miRNA，NKX2.3 是一种对 MAdCAM-1 表达至关重要的转录因子。综上所述，我们的研究提出，表达α4β7的T外泌体将自身分布到小肠并改变微环境组织的表达，从而排除任何随后的淋巴细胞归巢。这可能代表了一种新的机制，通过该机制，过量的淋巴细胞归巢到肠组织中被缩小。
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 alpha 4 beta 7 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 alpha 4 beta 7-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 alpha 4 beta 7-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.