HIF-1α-MSC外泌体调控Treg/Th17平衡诱导VCA免疫耐受的作用及其机制研究

如何有效诱导VCA免疫耐受是目前临床亟待解决的难题。研究表明HIF-1α可通过影响Treg/Th17平衡进行免疫调节。课题组前期研究发现MSC外泌体具有诱导免疫耐受的作用。然而过表达HIF-1α的MSC外泌体能否更有效的诱导VCA免疫耐受尚不明确。研究证实过表达HIF-1α的MSC可提高其免疫调节作用，而外泌体的功能与其母细胞的表达产物密切相关；据此推测，过表达HIF-1α的MSC外泌体能更有效的诱导VCA免疫耐受，其机制可能为HIF-1α调控FoxP3、 RORγt的表达从而影响Treg/Th17平衡。本研究拟采用基因重组技术构建过表达HIF-1α的MSC外泌体，利用超级显微外科技术建立VCA模型，探究其与FoxP3、 RORγt表达水平及Treg/Th17平衡的相关性，旨在阐明过表达HIF-1α的MSC外泌体诱导VCA免疫耐受的作用与分子机制，为临床诱导VCA免疫耐受提供一种新的策略。

The immune tolerance induction of vascularized composite allotransplantation (VCA) is unresolved in current clinical work. There studies suggested that HIF-1α could influence the balance of Treg/Th17 has played a vital role in immune tolerance. Our Pre-Experiment discovered that MSC harbor the potential of regulating immunity. However, whether the exosomes from HIF-1α highly expressed MSC can induce tolerance remain unclear. There are studies show that HIF-1α expression could up-regulate the immune regulation ability of MSC, and function of exosome is closely related to the products of MSC. Thus, we hypothesize exosomes secreted by MSC with HIF-1α modification are even more potent in immune tolerance induction. The mechanism could be that HIF-1α could influence Treg/Th17 ratio via regulating Foxp3, RORγt expression. Our study is designed to produce exosomes from HIF-1α highly expressed MSC via gene recombination and knockout technique, and to construct VCA model through super mirco-technology, so as to investigate the relativity among Foxp3, RORγt expression and Treg/Th17 ratio, which would provide the underlying immune induction mechanism of exosomes secreted by MSC with HIF-1α and further shine light upon development of a novel strategy of inducing VCA tolerance in clinical work.