PMID- 29523215
OWN - NLM
STAT- MEDLINE
DCOM- 20190128
LR  - 20190128
IS  - 1757-6512 (Electronic)
IS  - 1757-6512 (Linking)
VI  - 9
IP  - 1
DP  - 2018 Mar 9
TI  - Hydrogen sulfide promotes immunomodulation of gingiva-derived mesenchymal stem 
      cells via the Fas/FasL coupling pathway.
PG  - 62
LID - 10.1186/s13287-018-0804-6 [doi]
LID - 62
AB  - BACKGROUND: Mesenchymal stem cells derived from gingiva (GMSCs) display profound 
      immunomodulation properties in addition to self-renewal and multilineage 
      differentiation capacities. Hydrogen sulfide (H(2)S) is not only an environmental 
      pollutant, but also is an important biological gas transmitter in health and 
      disease. METHODS: We used an in-vitro coculture system and a mouse colitis model 
      to compare the immunomodulatory effects between control and H(2)S-deficient 
      GMSCs. The flow cytometry analysis was used for T-cell apoptosis and T-helper 17 
      (Th17) and regulatory T (Treg) cell differentiation. RESULTS: We revealed that 
      GMSCs exerted their immunomodulatory effect by inducing T-cell apoptosis, 
      promoting Treg cell polarization, and inhibiting Th17 cell polarization in vitro. 
      The levels of H(2)S regulated the immunomodulatory effect of GMSCs. Mechanically, 
      H(2)S deficiency downregulated the expression of Fas in GMSCs, resulting in 
      reduced secretion of monocyte chemotactic protein 1 (MCP-1), which in turn led to 
      decreased T-cell migration to GMSCs mediated by MCP-1. Moreover, H(2)S deficiency 
      downregulated the expression of Fas ligand (FasL) in GMSCs. The Fas/FasL 
      coupling-induced T-cell apoptosis by GMSCs was attenuated in H(2)S-deficient 
      GMSCs. Consistent with this, H(2)S-deficient GMSCs showed attenuated therapeutic 
      effects on colitis in vivo, which could be restored by treatment with the H(2)S 
      donor, NaHS. CONCLUSIONS: These findings showed that H(2)S was required to 
      maintain immunomodulation of GMSCs, which was mediated by Fas/FasL 
      coupling-induced T-cell apoptosis.
FAU - Yang, Ruili
AU  - Yang R
AUID- ORCID: 0000-0002-3283-9893
AD  - Department of Orthodontics, Peking University School and Hospital of Stomatology, 
      National Engineering Laboratory for Digital and Material Technology of 
      Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing, 100081, 
      China. ruiliyangabc@163.com.
AD  - Department of Anatomy and Cell Biology, University of Pennsylvania, School of 
      Dental Medicine, Philadelphia, PA, 19104, USA. ruiliyangabc@163.com.
FAU - Yu, Tingting
AU  - Yu T
AD  - Department of Orthodontics, Peking University School and Hospital of Stomatology, 
      National Engineering Laboratory for Digital and Material Technology of 
      Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing, 100081, 
      China.
AD  - Department of Anatomy and Cell Biology, University of Pennsylvania, School of 
      Dental Medicine, Philadelphia, PA, 19104, USA.
FAU - Liu, Dawei
AU  - Liu D
AD  - Department of Orthodontics, Peking University School and Hospital of Stomatology, 
      National Engineering Laboratory for Digital and Material Technology of 
      Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing, 100081, 
      China.
AD  - Department of Anatomy and Cell Biology, University of Pennsylvania, School of 
      Dental Medicine, Philadelphia, PA, 19104, USA.
FAU - Shi, Songtao
AU  - Shi S
AD  - Department of Anatomy and Cell Biology, University of Pennsylvania, School of 
      Dental Medicine, Philadelphia, PA, 19104, USA.
FAU - Zhou, Yanheng
AU  - Zhou Y
AD  - Department of Orthodontics, Peking University School and Hospital of Stomatology, 
      National Engineering Laboratory for Digital and Material Technology of 
      Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing, 100081, 
      China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180309
PL  - England
TA  - Stem Cell Res Ther
JT  - Stem cell research & therapy
JID - 101527581
RN  - 0 (Fas Ligand Protein)
RN  - 0 (fas Receptor)
RN  - YY9FVM7NSN (Hydrogen Sulfide)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Cells, Cultured
MH  - Fas Ligand Protein/*metabolism
MH  - Gingiva/cytology
MH  - Hydrogen Sulfide/*pharmacology
MH  - *Immunomodulation
MH  - Mesenchymal Stem Cells/*drug effects/immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - T-Lymphocytes/*immunology
MH  - fas Receptor/metabolism
PMC - PMC5845196
OTO - NOTNLM
OT  - Cell signaling
OT  - Fas pathway
OT  - Immunity
OT  - Infectious diseases
OT  - Stem cells
COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: All animal experiments were performed 
      under institutionally approved protocols for the use of animal research at 
      University of Pennsylvania (IACUC# 805478) and Peking University (#LA2012-65). 
      CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: The authors declare 
      that they have no competing interests. PUBLISHER'S NOTE: Springer Nature remains 
      neutral with regard to jurisdictional claims in published maps and institutional 
      affiliations.
EDAT- 2018/03/11 06:00
MHDA- 2019/01/29 06:00
PMCR- 2018/03/09
CRDT- 2018/03/11 06:00
PHST- 2017/11/13 00:00 [received]
PHST- 2018/02/11 00:00 [accepted]
PHST- 2018/02/05 00:00 [revised]
PHST- 2018/03/11 06:00 [entrez]
PHST- 2018/03/11 06:00 [pubmed]
PHST- 2019/01/29 06:00 [medline]
PHST- 2018/03/09 00:00 [pmc-release]
AID - 10.1186/s13287-018-0804-6 [pii]
AID - 804 [pii]
AID - 10.1186/s13287-018-0804-6 [doi]
PST - epublish
SO  - Stem Cell Res Ther. 2018 Mar 9;9(1):62. doi: 10.1186/s13287-018-0804-6.