Pseudomonas aeruginosa outer membrane vesicles ameliorates lung ischemia-reperfusion injury by regulating the balance of regulatory T cells and Th17 cells through Tim-3 and TLR4/NF-kappa B pathway

作者全名："Liu, Bo; Ding, Fengxia; Cao, Ding; Liu, Jiang; Wang, Yaping; Wu, Chun"

作者地址："[Liu, Bo; Wu, Chun] Minist Educ, Key Lab Child Dev & Disorders, Dept Cardiothorac Surg, 136,Zhongshan 2nd Rd, Chongqing 400014, Peoples R China; [Liu, Bo; Ding, Fengxia; Liu, Jiang; Wang, Yaping; Wu, Chun] Natl Clin Res Ctr Child Hlth & Disorders, 136,Zhongshan 2nd Rd, Chongqing 400014, Peoples R China; [Liu, Bo; Ding, Fengxia; Liu, Jiang; Wang, Yaping; Wu, Chun] Chongqing Med Univ, China Int Sci & Technol Cooperat Base Child Dev &, Childrens Hosp, 136,Zhongshan 2nd Rd, Chongqing 400014, Peoples R China; [Ding, Fengxia; Liu, Jiang; Wang, Yaping] Chongqing Med Univ, Minist Educ, Key Lab Child Dev & Disorders, Dept Resp Med, Chongqing, Peoples R China; [Cao, Ding] Chongqing Med Univ, Affiliated Hosp 2, Chongqing Key Lab Hepatobiliary Surg, Dept Hepatobiliary Surg, Chongqing, Peoples R China; [Liu, Bo; Ding, Fengxia; Liu, Jiang; Wang, Yaping] Chongqing Med Univ, Chongqing Engn Res Ctr Stem Cell Therapy, Chongqing Key Lab Pediat, Chongqing, Peoples R China"

通信作者："Liu, B (corresponding author), Minist Educ, Key Lab Child Dev & Disorders, Dept Cardiothorac Surg, 136,Zhongshan 2nd Rd, Chongqing 400014, Peoples R China.; Liu, B (corresponding author), Natl Clin Res Ctr Child Hlth & Disorders, 136,Zhongshan 2nd Rd, Chongqing 400014, Peoples R China.; Liu, B (corresponding author), Chongqing Med Univ, China Int Sci & Technol Cooperat Base Child Dev &, Childrens Hosp, 136,Zhongshan 2nd Rd, Chongqing 400014, Peoples R China.; Liu, B (corresponding author), Chongqing Med Univ, Chongqing Engn Res Ctr Stem Cell Therapy, Chongqing Key Lab Pediat, Chongqing, Peoples R China."

来源：INFLAMMATION RESEARCH

ESI学科分类：IMMUNOLOGY

WOS号：WOS:000669758500001

JCR分区：Q2

影响因子：6.7

年份：2021

卷号：70

期号：8

开始页：891

结束页：902

文献类型：Article

关键词：Outer membrane vesicle; Lung; Ischemia-reperfusion injury; T cell

摘要："Objective Regulatory T cells (Tregs) and T helper (Th) 17 cells are two subsets of CD4 + T cells with opposite effects which play a crucial role in the pathogenesis of lung injury. In this study, we aim to investigate the protective effect of Pseudomonas aeruginosa outer membrane vesicles (OMVs) preconditioning on lung ischemia-reperfusion (I/R) injury and potential mechanisms. Methods Pathogen-free C57BL/6 mice were randomly divided into four groups: control, Control + OMVs, I/R and I/R + OMVs groups. Bronchoalveolar lavage fluid (BALF), serum, and lung tissues were collected and analyzed for pathophysiology and immune mechanism. Results OMVs not only attenuated tissue injury and respiratory physiologic function but also mediated the downregulation of lung wet-to-dry weight ratio and the reduction of total protein concentration. The numbers of total cells, macrophages, neutrophils, and lymphocytes were markedly decreased in the I/R mice following OMVs preconditioning. OMVs also decreased inflammatory cytokines associated with CD4 + T cells in both BALF and serum. In addition, the level of Tregs and its transcription factor forkhead box P3 (Foxp3) were significantly increased, while the level of Th17 cells and its transcription factor retinoid-related orphan receptor gamma (ROR gamma t) were significantly decreased following OMVs preconditioning. In the process of exploring the underlying protection mechanisms of OMVs, we found that OMVs preconditioning significantly reduced protein expression of Toll-like receptor 4 (TLR4), which in turn not only inactivated myeloid differentiation factor 88 (MyD88) and Phosphorylated nuclear factor kappa B (p-NF-kappa B), but also simultaneously increased the levels of T-cell immunoglobulin and mucin domain-containing protein 3 (Tim-3). Conclusions These results suggest that OMVs preconditioning may ameliorate lung I/R injury by regulating the balance of Tregs and Th17 cells through Tim-3 and TLR4/NF-kappa B pathway."

基金机构：National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81800618]

基金资助正文：This work was supported by National Natural Science Foundation of China Grant 81800618.