Departmental Papers (Dental)

Document Type

Journal Article

Date of this Version

5-4-2012

Publication Source

Cell Stem Cell

Volume

10

Issue

5

Start Page

544

Last Page

555

DOI

10.1016/j.stem.2012.03.007

Abstract

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.

Copyright/Permission Statement

This is a post-peer-review, pre-copyedit version of an article published in Cell Stem Cell. The final authenticated version is available online at: http://dx.doi.org/10.1016/j.stem.2012.03.007

Comments

At the time of publication, author Chider Chen was affiliated with the University of Southern California. Currently, he is a faculty member at the School of Dental Medicine at the University of Pennsylvania.

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Date Posted: 25 February 2022

This document has been peer reviewed.