Self-renewing resident cardiac macrophages limit adverse remodeling following myocardial infarction
By Sarah A. Dick, J. A. Macklin, S. Nejat, A. Momen, X. Clemente-Casares, Marwan G. Althagafi, Jinmiao Chen, Crystal Kantores, Siyavash Hosseinzadeh, Laura Aronoff and 11 more. Nature Immunology, 2018
766 citations recorded by the source corpus.
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. Epelman and colleagues use fate mapping and single-cell transcriptomics to describe the dynamics of resident and recruited cardiac macrophages during ischemic injury.
Subfields: Cardiology and Cardiovascular Medicine, Molecular Biology, Surgery
View Paper: https://www.semanticscholar.org/paper/aee5e6bead24e8302864e4cfc1e76385abf8ec0c
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Citations in the corpus
- The role of macrophages in the resolution of inflammation. (2019, background): “Investigators have identified four distinct populations of tissue-resident macrophages in the heart, which have been shown to play divergent roles in tissue injury and repair (7, 20).”
- Two distinct interstitial macrophage populations coexist across tissues in specific subtissular niches (2019, result): “Specially in the heart, Lyve1MHCII MRTMs appear to have almost no exchange with monocytes in our S100a4-Rosa model, which is in agreement with a recent study showing that such populations mostly self-renew with no contribution ofmonocytes (53).”