TREM2(hi) resident macrophages protect the septic heart by maintaining cardiomyocyte homeostasis.
TREM2(hi) resident macrophages protect the septic heart by maintaining cardiomyocyte homeostasis.
复制标题
DOI：
10.1038/s42255-022-00715-5
复制
发表时间：
2023-01
影响因子：
20.8
通讯作者：
Fang, Xiangming
中科院分区：
文献类型：
--
作者：
Zhang, Kai;Wang, Yang;Chen, Shiyu;Mao, Jiali;Jin, Yue;Ye, Hui;Zhang, Yan;Liu, Xiwang;Gong, Chenchen;Cheng, Xuejun;Huang, Xiaoli;Hoeft, Andreas;Chen, Qixing;Li, Xuekun;Fang, Xiangming
脓毒症诱发的心肌病（SICM）在脓毒症患者中很常见，死亡率很高，其特征是免疫反应异常。由于细胞的异质性，理解免疫细胞亚群在SICM中的作用一直具有挑战性。在这里，我们确定了一个独特的心脏驻留巨噬细胞亚群，称为CD163+RETNLA+（Mac1），它在脓毒症期间进行自我更新，可以有针对性地预防SICM。通过将单细胞RNA测序与脓毒症小鼠模型中的命运作图相结合，我们证明了Mac1亚群具有丰富的内吞作用的独特转录组特征，并显示出高表达的TREM2（TREM2hi）。TREM2hi Mac1细胞积极地抑制心肌细胞排出的功能障碍的线粒体。巨噬细胞中的Trem2缺陷损害Mac1亚群的自我更新能力，并因此导致受损线粒体的消除缺陷、心脏组织中的过度炎症反应、心功能障碍恶化和存活率降低。值得注意的是，心包内施用TREM2hi Macl细胞预防SICM。我们的研究结果表明，TREM2hi Mac1细胞的调节可以作为SICM的治疗策略。Zhang等人鉴定了一种独特的心脏驻留巨噬细胞群体，其可能是脓毒症诱导的心肌病的潜在治疗策略。
Sepsis-induced cardiomyopathy (SICM) is common in septic patients with a high mortality and is characterized by an abnormal immune response. Owing to cellular heterogeneity, understanding the roles of immune cell subsets in SICM has been challenging. Here we identify a unique subpopulation of cardiac-resident macrophages termed CD163+RETNLA+ (Mac1), which undergoes self-renewal during sepsis and can be targeted to prevent SICM. By combining single-cell RNA sequencing with fate mapping in a mouse model of sepsis, we demonstrate that the Mac1 subpopulation has distinct transcriptomic signatures enriched in endocytosis and displays high expression of TREM2 (TREM2hi). TREM2hi Mac1 cells actively scavenge cardiomyocyte-ejected dysfunctional mitochondria. Trem2 deficiency in macrophages impairs the self-renewal capability of the Mac1 subpopulation and consequently results in defective elimination of damaged mitochondria, excessive inflammatory response in cardiac tissue, exacerbated cardiac dysfunction and decreased survival. Notably, intrapericardial administration of TREM2hi Mac1 cells prevents SICM. Our findings suggest that the modulation of TREM2hi Mac1 cells could serve as a therapeutic strategy for SICM. Zhang et al. identify a unique population of cardiac-resident macrophages that could be a potential therapeutic strategy for sepsis-induced cardiomyopathy.
登录
查看更多内容
IRF3和I型干扰物为心肌梗死提供了致命的反应。
影响因子：
82.9
作者：
King KR;Aguirre AD;Ye YX;Sun Y;Roh JD;Ng RP Jr;Kohler RH;Arlauckas SP;Iwamoto Y;Savol A;Sadreyev RI;Kelly M;Fitzgibbons TP;Fitzgerald KA;Mitchison T;Libby P;Nahrendorf M;Weissleder R
通讯作者：
Weissleder R
影响因子：
30.5
作者：
Dick, Sarah A.;Macklin, Jillian A.;Epelman, Slava
通讯作者：
Epelman, Slava
影响因子：
38.9
作者：
Ammann, P;Fehr, T;Bertel, O
通讯作者：
Bertel, O
DOI：
10.1152/ajpregu.00432.2003
发表时间：
2004-03-01
影响因子：
2.8
作者：
Brealey, D;Karyampudi, S;Singer, M
通讯作者：
Singer, M
影响因子：
168.9
作者：
Brechot, Nicolas;Hajage, David;Combes, Alain
通讯作者：
Combes, Alain