Document Detail


Mesenchymal-stem-cell-induced immunoregulation involves FAS-ligand-/FAS-mediated T cell apoptosis.
MedLine Citation:
PMID:  22542159     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Kentaro Akiyama; Chider Chen; DanDan Wang; Xingtian Xu; Cunye Qu; Takayoshi Yamaza; Tao Cai; WanJun Chen; Lingyun Sun; Songtao Shi
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't     Date:  2012-04-26
Journal Detail:
Title:  Cell stem cell     Volume:  10     ISSN:  1875-9777     ISO Abbreviation:  Cell Stem Cell     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-05-07     Completed Date:  2012-09-07     Revised Date:  2014-09-14    
Medline Journal Info:
Nlm Unique ID:  101311472     Medline TA:  Cell Stem Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  544-55     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00962923
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD95 / metabolism*
Apoptosis
Bone Marrow Cells / immunology
Chemokine CCL2 / metabolism
Colitis / chemically induced,  immunology*,  therapy
Dextran Sulfate / administration & dosage
Fas Ligand Protein / genetics,  metabolism*
Humans
Immune Tolerance
Immunotherapy*
Mesenchymal Stem Cell Transplantation
Mesenchymal Stromal Cells / immunology*
Mice
Mice, Knockout
Microfilament Proteins / genetics
Scleroderma, Systemic / genetics,  immunology*,  therapy
T-Lymphocyte Subsets / immunology
T-Lymphocytes, Regulatory / immunology
Transforming Growth Factor beta / immunology,  metabolism
Grant Support
ID/Acronym/Agency:
R01 DE017449/DE/NIDCR NIH HHS; R01 DE017449-05/DE/NIDCR NIH HHS; R01 DE019413/DE/NIDCR NIH HHS; R01 DE019413/DE/NIDCR NIH HHS; R01 DE019413-02/DE/NIDCR NIH HHS; R01 DE019932/DE/NIDCR NIH HHS; R01 DE019932/DE/NIDCR NIH HHS; R01 DE019932-03/DE/NIDCR NIH HHS; R01DE017449/DE/NIDCR NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD95; 0/Ccl2 protein, mouse; 0/Chemokine CCL2; 0/Fas Ligand Protein; 0/Microfilament Proteins; 0/Transforming Growth Factor beta; 0/fibrillin; 9042-14-2/Dextran Sulfate
Comments/Corrections
Comment In:
Cell Stem Cell. 2012 May 4;10(5):485-7   [PMID:  22560070 ]

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