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

0301 basic medicine Cell signaling Medicine (General) Fas Ligand Protein T-Lymphocytes Gingiva Apoptosis Stem cells QD415-436 Biochemistry Immunomodulation Mice 03 medical and health sciences R5-920 Fas pathway Animals Hydrogen Sulfide fas Receptor Cells, Cultured Research Immunity Mesenchymal Stem Cells 3. Good health Mice, Inbred C57BL Infectious diseases
DOI: 10.1186/s13287-018-0804-6 Publication Date: 2018-03-09T08:32:09Z
ABSTRACT
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.
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