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Cell Stem Cell
Systemic infusion of bone marrow mesenchymal stem cells (BMMSCs) shows therapeutic benefit for a variety of autoimmune diseases, but the underlying mechanisms are poorly understood. Here we show that in mice systemic infusion of BMMSCs induced transient T-cell apoptosis via the Fas ligand (FasL)-dependent Fas pathway and could ameliorate disease phenotypes in fibrillin-1 mutated systemic sclerosis (SS) and dextran sulfate sodium-induced experimental colitis. FasL−/− BMMSCs did not induce T-cell apoptosis in recipients, and could not ameliorate SS and colitis. Mechanistic analysis revealed that Fas-regulated monocyte chemotactic protein 1 (MCP-1) secretion by BMMSCs recruited T-cells for FasL-mediated apoptosis. The apoptotic T-cells subsequently triggered macrophages to produce high levels of TGFβ which in turn led to the upregulation of Tregs and, ultimately, to immune tolerance. These data therefore demonstrate a previously unrecognized mechanism underlying BMMSC-based immunotherapy involving coupling via Fas/FasL to induce T-cell apoptosis.
© <2012>. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
Akiyama, K., Chen, C., Wang, D., Xu, X., Qu, C., Yamaza, T., Cai, T., Chen, W., Sun, L., & Shi, S. (2012). Mesenchymal Stem Cell-Induced Immunoregulation Involves Fas Ligand/Fas-Mediated T Cell Apoptosis. Cell Stem Cell, 10 (5), 544-555. http://dx.doi.org/10.1016/j.stem.2012.03.007
Date Posted: 01 March 2022
This document has been peer reviewed.