Modulating donor mitochondrial fusion/fission delivers immunoprotective effects in cardiac transplantation.

ABSTRACT: Early insults associated with cardiac transplantation increase the immunogenicity of donor microvascular endothelial cells (ECs), which interact with recipient alloreactive memory T cells and promote responses leading to allograft rejection. Thus, modulating EC immunogenicity could potentially alter T cell responses. Recent studies have shown modulating mitochondrial fusion/fission alters immune cell phenotype. Here, we assess whether modulating mitochondrial fusion/fission reduces EC immunogenicity and alters EC-T cell interactions. By knocking down DRP1, a mitochondrial fission protein, or by using the small molecules M1, a fusion promoter, and Mdivi1, a fission inhibitor, we demonstrate that promoting mitochondrial fusion reduced EC immunogenicity to allogeneic CD8⁺ T cells,

SUBMITTER: Tran DT 

PROVIDER: S-EPMC8813895 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature