Single-cell transcriptome analysis reveals the regulatory effects of artesunate on splenic immune cells in polymicrobial sepsis

Chen, Jiayun1,2; He, Xueling1; Bai, Yunmeng2; Liu, Jing2; Wong, Yin Kwan3; Xie, Lulin2; Zhang, Qian2; Luo, Piao2; Gao, Peng1; Gu, Liwei1; Guo, Qiuyan1; Cheng, Guangqing1; Wang, Chen1; Wang, Jigang1,2

2023-07-01

10.1016/j.jpha.2023.02.006

JOURNAL OF PHARMACEUTICAL ANALYSIS   Impact Factor & Quartile

2095-1779

2214-0883

Sepsis is characterized by a severe and life-threatening host immune response to polymicrobial infection accompanied by organ dysfunction. Studies on the therapeutic effect and mechanism of immunomodulatory drugs on the sepsis-induced hyperinflammatory or immunosuppression states of various immune cells remain limited. This study aimed to investigate the protective effects and underlying mechanism of artesunate (ART) on the splenic microenvironment of cecal ligation and puncture-induced sepsis model mice using single-cell RNA sequencing (scRNA-seq) and experimental validations. The scRNA-seq analysis revealed that ART inhibited the activation of pro-inflammatory macrophages recruited during sepsis. ART could restore neutrophils' chemotaxis and immune function in the septic spleen. It inhibited the activation of T regulatory cells but promoted the cytotoxic function of natural killer cells during sepsis. ART also promoted the differentiation and activity of splenic B cells in mice with sepsis. These results indicated that ART could alleviate the inflammatory and/or immunosuppressive states of various immune cells involved in sepsis to balance the immune homeostasis within the host. Overall, this study provided a comprehensive investigation of the regulatory effect of ART on the splenic microenvironment in sepsis, thus contributing to the application of ART as adjunctive therapy for the clinical treatment of sepsis.& COPY; 2023 The Authors. Published by Elsevier B.V. on behalf of Xi'an Jiaotong University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Artesunate Sepsis Single-cell RNA sequencing Immunomodulatory activity

SCI

English

Corresponding

National Natural Science Foundation of China[2020YFE0205100] ; China Academy of Chinese Medical Sciences (CACMS) Innovation Fund, China["2020YFA0908000","2022YFC2303600"] ; Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences[CW202002] ; Science and Technology Foundation of Shenzhen, China Science and Technology Foundation of Shenzhen, China[ZYYCXTD-C-2020 02] ; Science and Technology Foundation of Shenzhen, China (Shenzhen Clinical Medical Research Center for Geriatric Diseases)["82141001","82274182","82074098","82173914"] ; National Key R amp;D Program of China Key Projects for International Cooperation on Science, Technology and Innovation["CI2021A05101","CI2021A05104"] ; Fundamental Research Funds for the Central Public Welfare Research Institutes, China[CI2021B014] ; Shenzhen Governmental Sustainable Development Fund, China[JCYJ20210324115800001] ; Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties, China[2020YFE0205100] ; null[ZZ14-YQ-050] ; null[ZZ14-YQ-051] ; null[ZZ14-YQ-052] ; null[ZZ14-FL-0 02] ; null[ZZ14-ND-010] ; null[ZZ15-ND-10] ; null[KCXFZ20201221173612034] ; null[ZDSYS201504301616234] ; null[SZGSP001]

Pharmacology & Pharmacy

Pharmacology & Pharmacy

WOS:001053179600001

ELSEVIER

Web of Science

1.China Acad Chinese Med Sci, Natl Resource Ctr Chinese Mat Med, State Key Lab Breeding Base Daodi Herbs, Beijing 100700, Peoples R China
2.Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Affiliated Hosp 1, Shenzhen Clin Res Ctr Geriatr, Shenzhen 518020, Guangdong, Peoples R China
3.Peking Univ, Shenzhen Hosp, Dept Gastroenterol, Shenzhen 518020, Guangdong, Peoples R China

Chen, Jiayun,He, Xueling,Bai, Yunmeng,et al. Single-cell transcriptome analysis reveals the regulatory effects of artesunate on splenic immune cells in polymicrobial sepsis[J]. JOURNAL OF PHARMACEUTICAL ANALYSIS,2023,13(7).

Chen, Jiayun.,He, Xueling.,Bai, Yunmeng.,Liu, Jing.,Wong, Yin Kwan.,...&Wang, Jigang.(2023).Single-cell transcriptome analysis reveals the regulatory effects of artesunate on splenic immune cells in polymicrobial sepsis.JOURNAL OF PHARMACEUTICAL ANALYSIS,13(7).

Chen, Jiayun,et al."Single-cell transcriptome analysis reveals the regulatory effects of artesunate on splenic immune cells in polymicrobial sepsis".JOURNAL OF PHARMACEUTICAL ANALYSIS 13.7(2023).