Hydrogen sulfide promotes immunomodulation of gingiva-derived mesenchymal stem cells via the Fas/FasL coupling pathway

Stem Cell Research & Therapy

Songtao Shi¹  Dawei Liu²  Tingting Yu²  Yanheng Zhou²  Ruili Yang² 

[1] Department of Anatomy and Cell Biology, University of Pennsylvania, School of Dental Medicine;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;

关键词: Cell signaling;    Fas pathway;    Immunity;    Stem cells;    Infectious diseases;   

DOI  :  10.1186/s13287-018-0804-6

来源: DOAJ

【 摘 要 】

Abstract Background Mesenchymal stem cells derived from gingiva (GMSCs) display profound immunomodulation properties in addition to self-renewal and multilineage differentiation capacities. Hydrogen sulfide (H2S) 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 H2S-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 H2S regulated the immunomodulatory effect of GMSCs. Mechanically, H2S 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, H2S deficiency downregulated the expression of Fas ligand (FasL) in GMSCs. The Fas/FasL coupling-induced T-cell apoptosis by GMSCs was attenuated in H2S-deficient GMSCs. Consistent with this, H2S-deficient GMSCs showed attenuated therapeutic effects on colitis in vivo, which could be restored by treatment with the H2S donor, NaHS. Conclusions These findings showed that H2S was required to maintain immunomodulation of GMSCs, which was mediated by Fas/FasL coupling-induced T-cell apoptosis.

【 授权许可】

Unknown