期刊
CELL STEM CELL
卷 10, 期 5, 页码 544-555出版社
CELL PRESS
DOI: 10.1016/j.stem.2012.03.007
关键词
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资金
- National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services [RO1DE017449, RO1 DE019932, RO1 DE019413]
- California Institute for Regenerative Medicine [RN1-00572]
- NIDCR
- NIH
- China Major International [81120108021]
- ClinicalTrials.gov [NCT00962923]
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 TGF beta, which in turn led to the upregulation of Ca4(+)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.
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