SAMSN1 causes sepsis immunosuppression by inducing macrophages to express coinhibitory molecules that cause T-cell exhaustion via KEAP1–NRF2 signaling DOI Creative Commons
Yao Li, Tingting Li, Fei Xiao

и другие.

Chinese Medical Journal, Год журнала: 2025, Номер unknown

Опубликована: Апрель 27, 2025

Abstract Background: Immunosuppression is closely related to the pathogenesis of sepsis, but underlying mechanisms have not yet been fully elucidated. In this study, we aimed examine role Sterile Alpha Motif, Src Homology 3 domain and nuclear localization signal 1 (SAMSN1) in sepsis elucidate its potential molecular mechanism induced immunosuppression. Methods: RNA sequencing databases were used validate SAMSN1 expression sepsis. The impact on was verified using gene knockout mice. Flow cytometry employed delineate how affects immunity focusing immune cell types T functions. Clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9)-mediated editing RAW264.7 macrophages enabled interrogation ’s regulatory effects essential macrophage functions, including proliferation phagocytic capacity. interaction between cells investigated line primary lines. Results: significantly increased patients with positively correlated mortality. Genetic deletion Samsn1 murine model improved survival, elevated cytolytic activity, activated signaling transduction. Concurrently, augmented capacity efficiency. macrophage, binds Kelch-like epichlorohydrin-associated (KEAP1), causing factor erythroid 2-related 2 (NRF2) dissociate from KEAP1–NRF2 complex translocate into nucleus. This promotes transcription coinhibitory molecules CD48/CD86/carcinoembryonic antigen adhesion molecule (CEACAM1), which bind their corresponding receptors natural killer receptor 2B4 (2B4)/CD152/T immunoglobulin mucin domain-containing (TIM3) surface cells, inducing T-cell exhaustion. Conclusions: adaptive phagocytic-proliferative dual function. Furthermore, it mediates axis, macrophages, leading novel immunosuppression potentially provides a candidate target for immunotherapy.

Язык: Английский

SAMSN1 causes sepsis immunosuppression by inducing macrophages to express coinhibitory molecules that cause T-cell exhaustion via KEAP1–NRF2 signaling DOI Creative Commons
Yao Li, Tingting Li, Fei Xiao

и другие.

Chinese Medical Journal, Год журнала: 2025, Номер unknown

Опубликована: Апрель 27, 2025

Abstract Background: Immunosuppression is closely related to the pathogenesis of sepsis, but underlying mechanisms have not yet been fully elucidated. In this study, we aimed examine role Sterile Alpha Motif, Src Homology 3 domain and nuclear localization signal 1 (SAMSN1) in sepsis elucidate its potential molecular mechanism induced immunosuppression. Methods: RNA sequencing databases were used validate SAMSN1 expression sepsis. The impact on was verified using gene knockout mice. Flow cytometry employed delineate how affects immunity focusing immune cell types T functions. Clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9)-mediated editing RAW264.7 macrophages enabled interrogation ’s regulatory effects essential macrophage functions, including proliferation phagocytic capacity. interaction between cells investigated line primary lines. Results: significantly increased patients with positively correlated mortality. Genetic deletion Samsn1 murine model improved survival, elevated cytolytic activity, activated signaling transduction. Concurrently, augmented capacity efficiency. macrophage, binds Kelch-like epichlorohydrin-associated (KEAP1), causing factor erythroid 2-related 2 (NRF2) dissociate from KEAP1–NRF2 complex translocate into nucleus. This promotes transcription coinhibitory molecules CD48/CD86/carcinoembryonic antigen adhesion molecule (CEACAM1), which bind their corresponding receptors natural killer receptor 2B4 (2B4)/CD152/T immunoglobulin mucin domain-containing (TIM3) surface cells, inducing T-cell exhaustion. Conclusions: adaptive phagocytic-proliferative dual function. Furthermore, it mediates axis, macrophages, leading novel immunosuppression potentially provides a candidate target for immunotherapy.

Язык: Английский

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