Single-cell transcriptome profiling of sepsis identifies HLA-DR^(low)S100A^(high)monocytes with immunosuppressive function
作者机构：Translational Medicine Research CenterMedical Innovation Research Division and the Fourth Medical Center of Chinese PLA General HospitalBei‑jing 100853China Department of Burn Surgerythe First Affiliated Hospital of Naval Medical UniversityShanghai 200433China Research Unit of Key Techniques for Treatment of Burns and Combined Burns and Trauma InjuryChinese Academy of Medical SciencesBeijing 100730China Department of General Surgerythe First Medical Center of Chinese PLA General HospitalBeijing 100853China Department of Neurosurgerythe First Medical Center of Chinese PLA General HospitalBeijing 100853China Department of Critical Care Medicinethe First Medical Center of Chinese PLA General HospitalBeijing 100853China Intensive Care UnitDalian Municipal Central Hospital Affiliated Dalian University of TechnologyDalian 116033LiaoningChina Department of Emergencythe Second Hospital of Hebei Medical UniversityShijiazhuang 050000China Department of Pulmonary and Criti‑cal Care MedicineBeijing Chaoyang HospitalCapital Medical UniversityBeijing 100020China.
出 版 物：《Military Medical Research》 (军事医学研究（英文版）)
年 卷 期：2023年第10卷第6期
页 面：778-797页
核心收录：
学科分类：100218[医学-急诊医学] 1002[医学-临床医学] 1010[医学-医学技术（可授医学、理学学位）] 10[医学]
基 金：supported by the Key Project of National Natural Science Foundation of China(82130062,82241062 and 81930057) the National Key Research and Development Program of China(2022YFA1104604) the Key Project of Military Medical Innovation Program of Chinese PLA(18CXZ026 and BLJ18J006) the CAMS Innovation Fund for Medical Sciences(2019-I2M-5-076)
主 题：Single-cell analysis Sepsis Immunosuppression S100A Human leukocyte antigen DR(HLA-DR) Monocytes Myeloid-derived suppressor cells(MDSCs) Paquinimod
摘 要：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 ***
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