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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
  • +7
  • Milica Lazarević,
  • Giuseppe Battaglia,
  • Bojan Jevtić,
  • Neda Đedović,
  • Valeria Bruno,
  • Eugenio Cavalli,
  • Djordje Miljkovic,
  • Ferdinando NICOLETTI,
  • Miljana Momcilovic,
  • Paolo Fagone
Milica Lazarević
University of Belgrade
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Giuseppe Battaglia
IRCCS Neurological Institute of Southern Italy NEUROMED
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Bojan Jevtić
University of Belgrade
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Neda Đedović
University of Belgrade
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Valeria Bruno
IRCCS Neurological Institute of Southern Italy NEUROMED
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Eugenio Cavalli
University of Catania
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Djordje Miljkovic
University of Belgrade
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Ferdinando NICOLETTI
University of Catania
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Miljana Momcilovic
University of Belgrade
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Paolo Fagone
University of Catania
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Peer review status:POSTED

18 May 2020Submitted to Clinical & Experimental Immunology
18 May 2020Assigned to Editor
18 May 2020Submission Checks Completed

Abstract

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.