Cyclosporine A regulates PMN-MDSCs viability and function through MPTP in acute GVHD: Old medication, new target

Transplant Cell Ther. 2022 Jul;28(7):411.e1-411.e9. doi: 10.1016/j.jtct.2022.04.010. Epub 2022 Apr 14.

Abstract

Myeloid-derived suppressor cells (MDSCs), a population of myeloid lineage cells with immunosuppressive capacity, can mitigate acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We previously found that the immunosuppressive function of polymorphonuclear population (PMN-MDSCs) was impaired in aGVHD milieu. The aim of this study was to explore the intrinsic mechanism regulating the fate and function of donor-derived PMN-MDSCs during allo-HSCT. We firstly found that mitochondrial permeability transition pore (MPTP) opened in the PMN-MDSCs in response to the intense inflammatory environment of aGVHD, which induced mitochondrial damage, oxidative stress, and apoptosis of PMN-MDSCs. Inhibiting MPTP opening by a traditional immunosuppressant, cyclosporine A (CsA), could restore the immunosuppressive function and viability of PMN-MDSCs in vitro and in vivo, which reveals a new mechanism of CsA application.

Keywords: Allo-HSCT; Cell death; MDSCs; MPTP; Mitochondria; aGVHD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cyclosporine / pharmacology
  • Graft vs Host Disease* / drug therapy
  • Humans
  • Immunosuppressive Agents / pharmacology
  • Mitochondrial Permeability Transition Pore
  • Myeloid-Derived Suppressor Cells*

Substances

  • Cyclosporine
  • Immunosuppressive Agents
  • Mitochondrial Permeability Transition Pore