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hUCMSC-derived exosomes protect against GVHD-induced endoplasmic reticulum stress in CD4+ T cells by targeting the miR-16-5p/ATF6/CHOP axis.
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- Author(s): Li, Weihan1,2 (AUTHOR); Si, Yaru1,3 (AUTHOR); Wang, Yueming1 (AUTHOR); Chen, Juntong3 (AUTHOR); Huo, Xingyu3 (AUTHOR); Xu, Pengzhan3 (AUTHOR); Jiang, Bingzhen3 (AUTHOR); Li, Zile3 (AUTHOR); Shang, Kangdi3 (AUTHOR); Luo, Qianqian1,3 (AUTHOR) ; Xiong, Yanlian1,3 (AUTHOR)
- Source:
International Immunopharmacology. Jun2024, Vol. 135, pN.PAG-N.PAG. 1p.- Subject Terms:
- Source:
- Additional Information
- Abstract: • hUCMSC-Exo promotes the differentiation of CD4+IL-10+T cells. • hUCMSC-Exo suppresses ER stress of CD4+ T cells by transfer miR-16-5p. • hUCMSC-Exo suppresses apoptosis of CD4+ T cells. • hUCMSC-Exo alleviates oxidative stress and inflammatory response during GVHD. 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. [ABSTRACT FROM AUTHOR]
- Abstract: Copyright of International Immunopharmacology is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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