Progranulin promotes regulatory T cells plasticity by mitochondrial metabolism through AMPK/PGC-1α pathway in ARDS

作者全名："Chen, Yanqing; Guo, Minkang; Xie, Ke; Lei, Ming; Chai, Yusen; Zhang, Zhengtao; Deng, Zhenhua; Peng, Qiaozhi; Cao, Ju; Lin, Shihui; Xu, Fang"

作者地址："[Chen, Yanqing; Guo, Minkang; Xie, Ke; Zhang, Zhengtao; Deng, Zhenhua; Peng, Qiaozhi; Lin, Shihui; Xu, Fang] Chongqing Med Univ, Affiliated Hosp 1, Dept Crit Care Med, Chongqing, Peoples R China; [Chen, Yanqing; Cao, Ju] Chongqing Med Univ, Affiliated Hosp 1, Dept Lab Med, Chongqing, Peoples R China; [Chen, Yanqing; Guo, Minkang] Chongqing Med Univ, Affiliated Hosp 1, Chongqing Key Lab Translat Med Major Metab Dis, Chongqing, Peoples R China; [Lei, Ming] Sun Yat Sen Univ, Affiliated Hosp 7, Dept Crit Care Med, Guangzhou, Peoples R China; [Chai, Yusen] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Anaesthesiol & Intens Care Med, Pulm Engn Grp, Dresden, Germany"

通信作者："Lin, SH; Xu, F (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Crit Care Med, Chongqing, Peoples R China."

来源：CLINICAL IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:001201876100001

JCR分区：Q2

影响因子：4.5

年份：2024

卷号：261

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Acute respiratory distress syndrome (ARDS); Progranulin (PGRN); Regulatory T cells (Tregs); Immunosenescence; Mitochondria; Metabolic reprogramming

摘要："As the aging population increases, the focus on elderly patients with acute respiratory distress syndrome (ARDS) is also increasing. In this article, we found progranulin (PGRN) differential expression in ARDS patients and healthy controls, even in young and old ARDS patients. Its expression strongly correlates with several cytokines in both young and elderly ARDS patients. PGRN has comparable therapeutic effects in young and elderly mice with lipopolysaccharide-induced acute lung injury, manifesting as lung injury, apoptosis, inflammation, and regulatory T cells (Tregs) differentiation. Considering that Tregs differentiation relies on metabolic reprogramming, we discovered that Tregs differentiation was mediated by mitochondrial function, especially in the aged population. Furthermore, we demonstrated that PGRN alleviated the mitochondrial damage during Tregs differentiation through the AMPK/PGC-1 alpha pathway in T cells. Collectively, PGRN may regulate mitochondria function to promote Tregs differentiation through the AMPK/PGC-1 alpha pathway to improve ARDS."

基金机构："National Natural Science Foundation of China [82172161, 81801894]; Chongqing Medical Scientific Research Project (Joint Project of Chongqing Health Commission and Science and Technology Bureau) [2023ZDXM004]; Lump -Sum Funding System of Chongqing Talent Program [cstc2022ycjh-bgzxm0131]; Doctoral Program of the First Affiliated Hospital of Chongqing Medical University [CYYY- BSYJSCXXM-202304, CYYY-BSYJSCXXM-202301]"

基金资助正文："This work was supported by the National Natural Science Foundation of China (82172161 to FX, 81801894 to SH-L) , Chongqing Medical Scientific Research Project (Joint Project of Chongqing Health Commission and Science and Technology Bureau) [2023ZDXM004 to FX] , Lump -Sum Funding System of Chongqing Talent Program [cstc2022ycjh-bgzxm0131 to FX] , and the Doctoral Program of the First Affiliated Hospital of Chongqing Medical University [CYYY- BSYJSCXXM-202304 to MK -G, CYYY-BSYJSCXXM-202301 to ZT-Z] ."