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. 2024 Oct;598(20):2581-2591.
doi: 10.1002/1873-3468.14999. Epub 2024 Aug 8.

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

Sumika Osa  1 , Yuki Enoki  1 , Daisuke Takahashi  2 , Victor Tuan Giam Chuang  3 , Kazuaki Taguchi  1 , Kazuaki Matsumoto  1
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Free article

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

Sumika Osa et al. FEBS Lett. 2024 Oct.
Free article

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.

Keywords: CTLA‐4; PD‐1; T‐cell immunosuppression; sarcopenia; sepsis; skeletal muscle atrophy.

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