Abstract：
Exosomes generated from mesenchymal stem cells (MSCs) are thought to be a unique therapeutic strategy for several autoimmune deficiency illnesses. The purpose of this study was to elucidate the protective effects of human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exo) on CD4+ T cells dysfunction during graft-versus-host disease (GVHD) and to identify the underlying processes involved. Here, we showed that hUCMSC-Exo treatment can effectively attenuate GVHD injury by alleviating redox metabolism disorders and inflammatory cytokine bursts in CD4+ T cells. Furthermore, hUCMSC-Exo ameliorate ER stress and ATF6/CHOP signaling-mediated apoptosis in CD4+ T cells and promote the development of CD4+IL-10+ T cells during GVHD. Moreover, downregulating miR-16-5p in hUCMSC-Exo impaired their ability to prevent CD4+ T cells apoptosis and weakened their ability to promote the differentiation of CD4+IL-10+ T cells. Collectively, the obtained data suggested that hUCMSC-Exo suppress ATF6/CHOP signaling-mediated ER stress and apoptosis in CD4+ T cells, enhance the differentiation of CD4+IL-10+ T cells, and reverse the imbalance of immune homeostasis in the GVHD process by transferring miR-16-5p. Our study provided further evidence that GVHD patients can benefit from hUCMSC-Exo-mediated therapy.
摘要：
由间充质干细胞（MSC）产生的外泌体被认为是几种自身免疫缺陷疾病的独特治疗策略。这项研究的目的是阐明人脐带间充质干细胞来源的外泌体（hUCMSC-Exo）对移植物抗宿主病（GVHD）期间CD4T细胞功能障碍的保护作用，并确定所涉及的潜在过程。这里,研究表明，hUCMSC-Exo治疗可通过减轻CD4+T细胞的氧化还原代谢紊乱和炎性细胞因子爆发，从而有效减轻GVHD损伤。此外，hUCMSC-Exo改善ER应激和ATF6/CHOP信号介导的CD4+T细胞凋亡，并促进CD4+IL-10+T细胞在GVHD期间的发育。此外，下调hUCMSC-Exo中的miR-16-5p会损害其阻止CD4+T细胞凋亡的能力，并削弱其促进CD4+IL-10+T细胞分化的能力。总的来说，获得的数据表明，hUCMSC-Exo抑制ATF6/CHOP信号介导的ER应激和CD4+T细胞凋亡，增强CD4+IL-10+T细胞的分化，并通过转移miR-16-5p逆转GVHD过程中免疫稳态的失衡。我们的研究提供了进一步的证据，证明GVHD患者可以从hUCMSC-Exo介导的治疗中受益。
