Tailoring hydrogen sulfide as therapeutic target in multiple sclerosis? Upregulation of tolerogenic pathways in dendritic cell and T cells from mice with EAE by the hydrogen sulfide donor GYY4137 and potentially impaired production of endogenous H2S in patients with multiple sclerosis

The aim of the study was to examine the in vitro effects of the slow-releasing H2S donor GYY4137 on immune cells involved in the pathogenesis of the central nervous system (CNS) autoimmune disease, multiple sclerosis (MS). GYY4137 specifically potentiated TGF-beta expression and production in dendritic cells and significantly reduced IFN-γ and IL-17 production in the lymph node and spinal cord T cells obtained from mice immunized with CNS antigens. Both the proportion of FoxP3+ regulatory CD4+ T cells in the lymph node cells, and the percentage of IL-17+ CD4+ T cells in the spinal cord cells were reduced upon culturing with GYY4137. Interestingly, peripheral blood mononuclear cells obtained from MS patients had lower expression of the H2S-producing enzyme, 3-mercaptopyruvate-sulfurtransferase (MPST), in comparison to those obtained from healthy donors. A significant inverse correlation between the expression of MPST and several pro-inflammatory factors was also observed. Further studies on the relevance of the observed results for the pathogenesis and therapy of MS are warranted.