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| Item Type: | Article |
|---|---|
| Title: | A growth factor-expressing macrophage subpopulation orchestrates regenerative inflammation via GDF-15 |
| Creators: |
Patsalos, A.  ORCID: https://orcid.org/0000-0002-9022-4985, Halasz, L. ORCID: https://orcid.org/0000-0003-4726-7012, Medina-Serpas, M.A. ORCID: https://orcid.org/0000-0003-0532-5413, Berger, W.K. ORCID: https://orcid.org/0000-0003-0727-7064, Daniel, B. ORCID: https://orcid.org/0000-0002-2410-8767, Tzerpos, P. ORCID: https://orcid.org/0000-0002-0398-0855, Kiss, M. ORCID: https://orcid.org/0000-0002-5649-0382, Nagy, G. ORCID: https://orcid.org/0000-0002-3273-731X, Fischer, C. ORCID: https://orcid.org/0000-0003-0329-2435, Simandi, Z. ORCID: https://orcid.org/0000-0001-8894-1259, Varga, T. ORCID: https://orcid.org/0000-0002-5303-1850 and Nagy, L. ORCID: https://orcid.org/0000-0001-6653-2155
|
| 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 Ly6C(high), infiltrating inflammatory Ly6C(high), and reparative Ly6C(low) 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]). |
| Keywords: | Cell Differentiation, Cultured Cells, Gene Expression Profiling, Growth Differentiation Factor 15, Inbred C57BL Mice, Inflammation, Intercellular Signaling Peptides and Proteins, Knockout Mice, Macrophages, Muscle Cells, Muscles, Myeloid Cells, RNA-Seq, Regeneration, Animals, Mice |
| Source: | Journal of Experimental Medicine |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Volume: | 219 |
| Number: | 1 |
| Page Range: | e20210420 |
| Date: | 3 January 2022 |
| Official Publication: | https://doi.org/10.1084/jem.20210420 |
| PubMed: | View item in PubMed |
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