CX3CR1型
巨噬细胞
CCR2型
心肌梗塞
抛物线性
单核细胞
生物
细胞生物学
主要组织相容性复合体
免疫学
内科学
心室重构
趋化因子
炎症
医学
趋化因子受体
免疫系统
遗传学
体外
作者
Sarah A. Dick,Jillian Macklin,Sara Nejat,Abdul Momen,Xavier Clemente-Casares,Marwan G. Althagafi,Jinmiao Chen,Crystal Kantores,Siyavash Hosseinzadeh,Laura Aronoff,Anthony Wong,Rysa Zaman,Iulia Barbu,Rickvinder Besla,Kory J. Lavine,Babak Razani,Florent Ginhoux,Mansoor Husain,Myron I. Cybulsky,Clinton S. Robbins,Slava Epelman
标识
DOI:10.1038/s41590-018-0272-2
摘要
Macrophages promote both injury and repair after myocardial infarction, but discriminating functions within mixed populations remains challenging. Here we used fate mapping, parabiosis and single-cell transcriptomics to demonstrate that at steady state, TIMD4+LYVE1+MHC-IIloCCR2- resident cardiac macrophages self-renew with negligible blood monocyte input. Monocytes partially replaced resident TIMD4-LYVE1-MHC-IIhiCCR2- macrophages and fully replaced TIMD4-LYVE1-MHC-IIhiCCR2+ macrophages, revealing a hierarchy of monocyte contribution to functionally distinct macrophage subsets. Ischemic injury reduced TIMD4+ and TIMD4- resident macrophage abundance, whereas CCR2+ monocyte-derived macrophages adopted multiple cell fates within infarcted tissue, including those nearly indistinguishable from resident macrophages. Recruited macrophages did not express TIMD4, highlighting the ability of TIMD4 to track a subset of resident macrophages in the absence of fate mapping. Despite this similarity, inducible depletion of resident macrophages using a Cx3cr1-based system led to impaired cardiac function and promoted adverse remodeling primarily within the peri-infarct zone, revealing a nonredundant, cardioprotective role of resident cardiac macrophages.
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