Mashima, Kiyomi published the artcileDimethyl fumarate ameliorates graft-versus-host disease by inhibiting T-cell metabolism and immune responses through a reactive oxygen species-dependent mechanism, Quality Control of 624-49-7, the publication is British Journal of Haematology (2022), 197(6), e78-e82, database is CAplus and MEDLINE.
Acute graft-vs.-host disease (GVHD) is among the leading causes of non-relapse mortality and morbidity after allogeneic haematopoietic stem cell transplantation. Di-Me fumarate (DMF), a fumaric acid derivative, is a novel therapeutic agent for relapsing multiple sclerosis and psoriasis. For instance, DMF succinates a key glycolytic enzyme, glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and irreversibly inactivates its enzymic activity, thereby downregulating aerobic glycolysis in CD4+ T cells. This study investigated whether, and if so, how DMF impairs the metabolism and immune responses of antigen-activated Tcells both in vitro and in vivo using a xenogeneic GVHD mouse model. While the number of CD4+ T cells decreased, the proportion of CD25+ FoxP3+ regulatory T cells (Treg) was higher in DMF-treated mice, and thus the total number of Tregs was equivalent in both groups. Given that DMF depletes intracellular GSH levels by forming succinated glutathione, causing dysregulated ROS accumulation in diverse immune cells and cancer cells, we investigated the redox status of T-cell receptor (TCR)- stimulated T cells after DMF treatment and evaluated the association between their metabolic profiles and effector T-cell function. Furthermore, NAC almost completely restored viability (Figure 2F), proliferation (Figure 2G), and interferon gamma (IFN-γ) production (Figure 2H) of TCR-stimulated T cells following DMF treatment. Clin. relevant GVHD model, which show better disease control and prolonged survival by DMF treatment, can be readily translated to clin. settings. Our findings will provide a mol. basis for potential future clin. applications of DMF for the prevention and treatment of GVHD.
British Journal of Haematology published new progress about 624-49-7. 624-49-7 belongs to esters-buliding-blocks, auxiliary class Inhibitor,Natural product, name is Dimethyl fumarate, and the molecular formula is C6H8O4, Quality Control of 624-49-7.
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