Targeting necroptosis in muscle fibers ameliorates inflammatory myopathies.

ABSTRACT: Muscle cell death in polymyositis is induced by CD8⁺ cytotoxic T lymphocytes. We hypothesized that the injured muscle fibers release pro-inflammatory molecules, which would further accelerate CD8⁺ cytotoxic T lymphocytes-induced muscle injury, and inhibition of the cell death of muscle fibers could be a novel therapeutic strategy to suppress both muscle injury and inflammation in polymyositis. Here, we show that the pattern of cell death of muscle fibers in polymyositis is FAS ligand-dependent necroptosis, while that of satellite cells and myoblasts is perforin 1/granzyme B-dependent apoptosis, using human muscle biopsy specimens of polymyositis patients and models of polymyositis in vitro and in vivo. Inhibition of necroptosis suppresses not only CD8⁺ cyto

SUBMITTER: Kamiya M 

PROVIDER: S-EPMC8748624 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature