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Single-cell transcriptome profiling of sepsis identifies HLA-DR^(low)S100A^(high)monocytes with immunosuppressive function

引用

Military Medical Research 2023年第6期10卷 778-797页

作者： Ren-Qi Yao Peng-Yue Zhao Zhi-Xuan Li Yu-Yang Liu Li-Yu Zheng Yu Duan Lu Wang Rong-Li Yang Hong-Jun Kang Ji-Wei Hao Jing-Yan Li Ning Dong Yao Wu Xiao-Hui Du Feng Zhu Chao Ren Guo-Sheng Wu Zhao-Fan Xia Yong-Ming Yao Translational Medicine Research Center Medical Innovation Research Division and the Fourth Medical Center of Chinese PLA General HospitalBei‑jing 100853China Department of Burn Surgery the First Affiliated Hospital of Naval Medical UniversityShanghai 200433China Research Unit of Key Techniques for Treatment of Burns and Combined Burns and Trauma Injury Chinese Academy of Medical SciencesBeijing 100730China Department of General Surgery the First Medical Center of Chinese PLA General HospitalBeijing 100853China Department of Neurosurgery the First Medical Center of Chinese PLA General HospitalBeijing 100853China Department of Critical Care Medicine the First Medical Center of Chinese PLA General HospitalBeijing 100853China Intensive Care Unit Dalian Municipal Central Hospital Affiliated Dalian University of TechnologyDalian 116033LiaoningChina Department of Emergency the Second Hospital of Hebei Medical UniversityShijiazhuang 050000China Department of Pulmonary and Criti‑cal Care Medicine Beijing Chaoyang HospitalCapital Medical UniversityBeijing 100020China.

Background Sustained yet intractable immunosuppression is commonly observed in septic patients,resulting in aggravated clinical ***,due to the substantial heterogeneity within septic patients,precise indicators in deciphering clinical trajectories and immunological alterations for septic patients remain largely *** We adopted cross-species,single-cell RNA sequencing(scRNA-seq)analysis based on two published datasets containing circulating immune cell profile of septic patients as well as immune cell atlas of murine model of *** cytometry,laser scanning confocal microscopy(LSCM)imaging and Western blotting were applied to identify the presence of S100A9^(+)monocytes at protein *** interrogate the immunosuppressive function of this subset,splenic monocytes isolated from septic wild-type or S100a9^(–/–)mice were co-cultured with naive CD4^(+)T cells,followed by proliferative *** inhibition of S100A9 was implemented using paquinimod via oral *** scRNA-seq analysis of human sepsis revealed substantial heterogeneity in monocyte compartments following the onset of sepsis,for which distinct monocyte subsets were enriched in disparate subclusters of septic *** identified a unique monocyte subset characterized by high expression of S100A family genes and low expression of human leukocyte antigen DR(HLA-DR),which were prominently enriched in septic patients and might exert immunosuppressive *** combining single-cell transcriptomics of murine model of sepsis with in vivo experiments,we uncovered a similar subtype of monocyte significantly associated with late sepsis and immunocompromised status of septic mice,corresponding to HLA-DR^(low)S100A^(high)monocytes in human ***,we found that S100A9^(+)monocytes exhibited profound immunosuppressive function on CD4^(+)T cell immune response and blockade of S100A9 using paquinimod could partially reverse sepsis-induced ***

关键词： Single-cell analysis Sepsis Immunosuppression S100A Human leukocyte antigen DR(HLA-DR) Monocytes Myeloid-derived suppressor cells(MDSCs) paquinimod

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