T‐cell immunosuppression in sepsis is augmented by sciatic denervation‐induced skeletal muscle atrophy

Abstract

Skeletal muscle atrophy is a known risk factor for immunosuppressive conditions and for a poor prognosis in sepsis. However, its immunopathology has not been experimentally elucidated. This study investigated the effects of skeletal muscle atrophy on the immunopathology of sepsis. Male C57BL/6J mice were subjected to sciatic denervation (DN) and caecal ligation and puncture (CLP) to induce muscle atrophy or sepsis. The macrophages, myeloid‐derived suppressor cells (MDSC), and T‐cells in peritoneal and spleen were analysed using flow cytometry. DN‐induced muscle atrophy did not affect macrophage and MDSC populations. In contrast, the percentage of cytotoxic T‐lymphocyte‐associated antigen (CTLA)‐4+ CD4+ T‐cells, programmed death (PD)‐1+ CD8+ T‐cells, regulatory T‐cells, and the CTLA‐4+ regulatory T‐cells was statistically significantly higher in DN‐CLP mice than in sham‐CLP mice. Skeletal muscle atrophy before sepsis triggers excessive T cell immunosuppression, which may contribute to the exacerbation of sepsis under skeletal muscle atrophy.