PMID- 22542159
OWN - NLM
STAT- MEDLINE
DCOM- 20120907
LR  - 20220822
IS  - 1875-9777 (Electronic)
IS  - 1934-5909 (Print)
IS  - 1875-9777 (Linking)
VI  - 10
IP  - 5
DP  - 2012 May 4
TI  - Mesenchymal-stem-cell-induced immunoregulation involves FAS-ligand-/FAS-mediated 
      T cell apoptosis.
PG  - 544-55
LID - 10.1016/j.stem.2012.03.007 [doi]
AB  - 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 TGFbeta, 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.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Akiyama, Kentaro
AU  - Akiyama K
AD  - Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University 
      of Southern California, 2250 Alcazar Street, CSA 103, Los Angeles, CA 90033, USA.
FAU - Chen, Chider
AU  - Chen C
FAU - Wang, DanDan
AU  - Wang D
FAU - Xu, Xingtian
AU  - Xu X
FAU - Qu, Cunye
AU  - Qu C
FAU - Yamaza, Takayoshi
AU  - Yamaza T
FAU - Cai, Tao
AU  - Cai T
FAU - Chen, WanJun
AU  - Chen W
FAU - Sun, Lingyun
AU  - Sun L
FAU - Shi, Songtao
AU  - Shi S
LA  - eng
SI  - ClinicalTrials.gov/NCT00962923
GR  - R01 DE017449/DE/NIDCR NIH HHS/United States
GR  - R01 DE019413/DE/NIDCR NIH HHS/United States
GR  - R01DE017449/DE/NIDCR NIH HHS/United States
GR  - R01 DE019413-02/DE/NIDCR NIH HHS/United States
GR  - R01 DE017449-05/DE/NIDCR NIH HHS/United States
GR  - ImNIH/Intramural NIH HHS/United States
GR  - R01 DE019932/DE/NIDCR NIH HHS/United States
GR  - R01 DE019932-03/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120426
PL  - United States
TA  - Cell Stem Cell
JT  - Cell stem cell
JID - 101311472
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (FBN1 protein, human)
RN  - 0 (Fas Ligand Protein)
RN  - 0 (Fbn1 protein, mouse)
RN  - 0 (Fibrillin-1)
RN  - 0 (Fibrillins)
RN  - 0 (Microfilament Proteins)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (fas Receptor)
RN  - 9042-14-2 (Dextran Sulfate)
SB  - IM
CIN - Cell Stem Cell. 2012 May 4;10(5):485-7. PMID: 22560070
MH  - Animals
MH  - Apoptosis
MH  - Bone Marrow Cells/immunology
MH  - Chemokine CCL2/metabolism
MH  - Colitis/chemically induced/*immunology/therapy
MH  - Dextran Sulfate/administration & dosage
MH  - Fas Ligand Protein/genetics/*metabolism
MH  - Fibrillin-1
MH  - Fibrillins
MH  - Humans
MH  - Immune Tolerance
MH  - *Immunotherapy
MH  - Mesenchymal Stem Cell Transplantation
MH  - Mesenchymal Stem Cells/*immunology
MH  - Mice
MH  - Mice, Knockout
MH  - Microfilament Proteins/genetics
MH  - Scleroderma, Systemic/genetics/*immunology/therapy
MH  - T-Lymphocyte Subsets/immunology
MH  - T-Lymphocytes, Regulatory/immunology
MH  - Transforming Growth Factor beta/immunology/metabolism
MH  - fas Receptor/*metabolism
PMC - PMC3348385
MID - NIHMS366975
EDAT- 2012/05/01 06:00
MHDA- 2012/09/08 06:00
PMCR- 2013/05/04
CRDT- 2012/05/01 06:00
PHST- 2011/10/11 00:00 [received]
PHST- 2012/02/11 00:00 [revised]
PHST- 2012/03/08 00:00 [accepted]
PHST- 2012/05/01 06:00 [entrez]
PHST- 2012/05/01 06:00 [pubmed]
PHST- 2012/09/08 06:00 [medline]
PHST- 2013/05/04 00:00 [pmc-release]
AID - S1934-5909(12)00124-5 [pii]
AID - 10.1016/j.stem.2012.03.007 [doi]
PST - ppublish
SO  - Cell Stem Cell. 2012 May 4;10(5):544-55. doi: 10.1016/j.stem.2012.03.007. Epub 
      2012 Apr 26.