A growth factor-expressing macrophage subpopulation orchestrates regenerative inflammation via GDF-15.
Andreas Patsalos,László Halász,Miguel A Medina-Serpas,Wilhelm K. Berger,Bence Daniel,Petros Tzerpos,Mate Kiss,Gergely Nagy,Cornelius Fischer,Zoltan Simandi,Tamas Varga,Laszlo Nagy,Laszlo Nagy +12 more
TLDR
In this article, the TGF-β superfamily member GDF-15 was identified as a component of the regeneration-promoting program (RPP), which is essential for proper repair.Abstract:
Muscle regeneration is the result of the concerted action of multiple cell types driven by the temporarily controlled phenotype switches of infiltrating monocyte-derived macrophages. Pro-inflammatory macrophages transition into a phenotype that drives tissue repair through the production of effectors such as growth factors. This orchestrated sequence of regenerative inflammatory events, which we termed regeneration-promoting program (RPP), is essential for proper repair. However, it is not well understood how specialized repair-macrophage identity develops in the RPP at the transcriptional level and how induced macrophage-derived factors coordinate tissue repair. Gene expression kinetics-based clustering of blood circulating Ly6Chigh, infiltrating inflammatory Ly6Chigh, and reparative Ly6Clow macrophages, isolated from injured muscle, identified the TGF-β superfamily member, GDF-15, as a component of the RPP. Myeloid GDF-15 is required for proper muscle regeneration following acute sterile injury, as revealed by gain- and loss-of-function studies. Mechanistically, GDF-15 acts both on proliferating myoblasts and on muscle-infiltrating myeloid cells. Epigenomic analyses of upstream regulators of Gdf15 expression identified that it is under the control of nuclear receptors RXR/PPARγ. Finally, immune single-cell RNA-seq profiling revealed that Gdf15 is coexpressed with other known muscle regeneration-associated growth factors, and their expression is limited to a unique subpopulation of repair-type macrophages (growth factor-expressing macrophages [GFEMs]).read more
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CD36, a signaling receptor and fatty acid transporter that regulates immune cell metabolism and fate
TL;DR: This review summarizes how CD36 dual functions determine immune cell functions and fates, which contribute to common diseases including atherosclerosis and tumor progression.
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Targeting SLC7A11 improves efferocytosis by dendritic cells and wound healing in diabetes
Sophia Maschalidi,Parul Mehrotra,Burcu Nur Keçeli,Hannah K L De Cleene,K. Lecomte,Renée Van der Cruyssen,Pauline Janssen,Jonathan J. Pinney,Geert van Loo,Dirk Elewaut,Ann Massie,Esther Hoste,Kodi S. Ravichandran +12 more
TL;DR: In this paper , the membrane transporter SLC7a11 acts as a molecular brake on efferocytosis, the process by which dying cells are removed, and that inhibiting SLC 7a11 function can accelerate wound healing.
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Targeting SLC7A11 improves efferocytosis by dendritic cells and wound healing in diabetes
Sophia Maschalidi,Parul Mehrotra,Burcu Nur Keçeli,Hannah K. L. Cleene,K. Lecomte,R. Cruyssen,Pauline Janssen,Jonathan J. Pinney,Geert van Loo,Dirk Elewaut,Ann Massie,Esther Hoste,Kodi S. Ravichandran +12 more
TL;DR: In this article , the membrane transporter SLC7a11 acts as a molecular brake on efferocytosis, the process by which dying cells are removed, and that inhibiting SLC 7a11 function can accelerate wound healing.
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Differences in muscle satellite cell dynamics during muscle hypertrophy and regeneration
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