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

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.

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.

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.

These findings showed that H₂S was required to maintain immunomodulation of GMSCs, which was mediated by Fas/FasL coupling-induced T-cell apoptosis.