دورية أكاديمية
Single-cell transcriptome profiling of sepsis identifies HLA-DR low S100A high monocytes with immunosuppressive function
| العنوان: | Single-cell transcriptome profiling of sepsis identifies HLA-DR low S100A high monocytes with immunosuppressive function |
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| المؤلفون: | 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 |
| المصدر: | Military Medical Research, Vol 10, Iss 1, Pp 1-20 (2023) |
| بيانات النشر: | BMC, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Medicine (General) LCC:Military Science |
| مصطلحات موضوعية: | Single-cell analysis, Sepsis, Immunosuppression, S100A, Human leukocyte antigen DR (HLA-DR), Monocytes, Medicine (General), R5-920, Military Science |
| الوصف: | Abstract Background Sustained yet intractable immunosuppression is commonly observed in septic patients, resulting in aggravated clinical outcomes. However, due to the substantial heterogeneity within septic patients, precise indicators in deciphering clinical trajectories and immunological alterations for septic patients remain largely lacking. Methods 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 sepsis. Flow cytometry, laser scanning confocal microscopy (LSCM) imaging and Western blotting were applied to identify the presence of S100A9+ monocytes at protein level. To interrogate the immunosuppressive function of this subset, splenic monocytes isolated from septic wild-type or S100a9 −/− mice were co-cultured with naïve CD4+ T cells, followed by proliferative assay. Pharmacological inhibition of S100A9 was implemented using Paquinimod via oral gavage. Results 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 patients. We 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 function. By 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 sepsis. Moreover, 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 immunosuppression. Conclusions This study identifies HLA-DR low S100A high monocytes correlated with immunosuppressive state upon septic challenge, inhibition of which can markedly mitigate sepsis-induced immune depression, thereby providing a novel therapeutic strategy for the management of sepsis. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2054-9369 |
| Relation: | https://doaj.org/toc/2054-9369 |
| DOI: | 10.1186/s40779-023-00462-y |
| URL الوصول: | https://doaj.org/article/a8f793824e8c44ee83a53b4acfbb846e |
| رقم الأكسشن: | edsdoj.8f793824e8c44ee83a53b4acfbb846e |
| قاعدة البيانات: | Directory of Open Access Journals |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 20549369 |
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| DOI: | 10.1186/s40779-023-00462-y |