hUCMSC-derived exosomes protect against GVHD-induced endoplasmic reticulum stress in CD4 + T cells by targeting the miR-16-5p/ATF6/CHOP axis.

Autor: Li W; Xu Rongxiang Regenerative Medicine Research Center, Binzhou Medical University, Yantai, PR China; Shanghai Mebo Life Science & Technology Co., Shanghai, PR China., Si Y; Department of Histology and Embryology, School of Basic Medicine, Binzhou Medical University, Yantai, PR China., Wang Y; Xu Rongxiang Regenerative Medicine Research Center, Binzhou Medical University, Yantai, PR China., Chen J; Department of Histology and Embryology, School of Basic Medicine, Binzhou Medical University, Yantai, PR China., Huo X; Department of Histology and Embryology, School of Basic Medicine, Binzhou Medical University, Yantai, PR China., Xu P; Department of Histology and Embryology, School of Basic Medicine, Binzhou Medical University, Yantai, PR China., Jiang B; Department of Histology and Embryology, School of Basic Medicine, Binzhou Medical University, Yantai, PR China., Li Z; Department of Histology and Embryology, School of Basic Medicine, Binzhou Medical University, Yantai, PR China., Shang K; Department of Histology and Embryology, School of Basic Medicine, Binzhou Medical University, Yantai, PR China., Luo Q; Department of Histology and Embryology, School of Basic Medicine, Binzhou Medical University, Yantai, PR China. Electronic address: qqluo2012@sina.com., Xiong Y; Xu Rongxiang Regenerative Medicine Research Center, Binzhou Medical University, Yantai, PR China; Department of Histology and Embryology, School of Basic Medicine, Binzhou Medical University, Yantai, PR China. Electronic address: xyl1988@bzmc.edu.cn.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2024 Jun 30; Vol. 135, pp. 112315. Date of Electronic Publication: 2024 May 27.
DOI: 10.1016/j.intimp.2024.112315
Abstrakt: 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.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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