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

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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

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Mesenchymal Stromal Cells
Bone Marrow
Apoptosis
Ligands
T-Lymphocytes
Systemic Scleroderma
Colitis
Immune Tolerance
Dextran Sulfate
Chemokine CCL2
Regulatory T-Lymphocytes
Immunotherapy
Autoimmune Diseases
Up-Regulation
Macrophages
Phenotype
Therapeutics

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine
  • Genetics

Cite this

Mesenchymal-stem-cell-induced immunoregulation involves FAS-ligand-/FAS-mediated T cell apoptosis. / Akiyama, Kentaro; Chen, Chider; Wang, Dandan; Xu, Xingtian; Qu, Cunye; Yamaza, Takayoshi; Cai, Tao; Chen, Wanjun; Sun, Lingyun; Shi, Songtao.

In: Cell Stem Cell, Vol. 10, No. 5, 04.05.2012, p. 544-555.

Research output: Contribution to journalArticle

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, vol. 10, no. 5, pp. 544-555. https://doi.org/10.1016/j.stem.2012.03.007
Akiyama, Kentaro ; Chen, Chider ; Wang, Dandan ; Xu, Xingtian ; Qu, Cunye ; Yamaza, Takayoshi ; Cai, Tao ; Chen, Wanjun ; Sun, Lingyun ; Shi, Songtao. / Mesenchymal-stem-cell-induced immunoregulation involves FAS-ligand-/FAS-mediated T cell apoptosis. In: Cell Stem Cell. 2012 ; Vol. 10, No. 5. pp. 544-555.
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