Mesenchymal-stem-cell-induced immunoregulation involves FAS-ligand-/FAS-mediated T cell apoptosis

Kentaro Akiyama, Chider Chen, Dandan Wang, Xingtian Xu, Cunye Qu, Takayoshi Yamaza, Tao Cai, Wanjun Chen, Lingyun Sun, Songtao Shi

Research output: Contribution to journalArticle

336 Citations (Scopus)

Abstract

Systemic infusion of bone marrow mesenchymal stem cells (BMMSCs) yields 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 CD4 +CD25 +Foxp3 + regulatory T cells and, ultimately, immune tolerance. These data therefore demonstrate a previously unrecognized mechanism underlying BMMSC-based immunotherapy involving coupling via FAS/FASL to induce T cell apoptosis.

Original languageEnglish
Pages (from-to)544-555
Number of pages12
JournalCell Stem Cell
Volume10
Issue number5
DOIs
Publication statusPublished - May 4 2012

    Fingerprint

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine
  • Genetics

Cite this

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. https://doi.org/10.1016/j.stem.2012.03.007