ArticleThe Journal of experimental medicine2022
A growth factor-expressing macrophage subpopulation orchestrates regenerative inflammation via GDF-15.
Article in The Journal of experimental medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
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Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.
- Circulating level of growth-differentiation factor 15 and the functional outcome after acute ischemic stroke: a systematic review and meta-analysis.Head & face medicine · 2024Pooled it
- Review
- BACH1 orchestrates macrophage state transitions to coordinate regenerative inflammation.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Sema4A Protects Against Muscle Atrophy and Promotes Repair by Regulating Intracellular Metabolic Signalling.Journal of cachexia, sarcopenia and muscle · 2026Article
- Gdf15 expression in thermogenic adipocytes regulates diet-induced weight gain in a sex-dependent manner.Molecular medicine (Cambridge, Mass.) · 2026Article
- Inflammation and wound healing: a comprehensive overview of mechanisms, therapeutic strategies, and translational perspectives.Biomarker research · 2026Review
- Macrophage and fibro-adipogenic progenitor communication in skeletal muscle regeneration: tissue homeostasis and pathogenic remodeling.Journal of leukocyte biology · 2026Review
- Single-cell transcriptomics highlights macrophage-driven regulation of EndMT and repair in injured muscle.Communications biology · 2026Article
- Cellular senescence in skeletal muscle regeneration.Cell regeneration (London, England) · 2026Review
- GFRAL is required to mediate changes in systemic metabolism in response to mitochondrial stress in brown adipose tissue.Journal of molecular medicine (Berlin, Germany) · 2026Article
- Perivascular mesenchymal cells instruct ST2+ reparative macrophages to promote endovascular injury-induced neointimal hyperplasia in mice.Nature communications · 2026Article
- Activin A secretion by muscle-repairing macrophages induces heterotopic ossification in mice.The Journal of clinical investigation · 2026Article
- A GDF-15-GFRAL axis controls autoimmune T cell responses during neuroinflammation.Nature immunology · 2026Article
- Macrophage Infiltration, Activation, and Therapeutic Implication in Skeletal Muscle Injury and Repair.International journal of molecular sciences · 2026Review
- ST2 Signaling Regulates Innate Immune Responses in Kidney Injury.bioRxiv : the preprint server for biology · 2026Article
- From lipid switch to tissue repair: how resolvins reprogram macrophage polarization and function.Immunometabolism (Cobham, Surrey) · 2026Review
- The gene regulatory networks shaping macrophage plasticity and altered function in fibrosis.Frontiers in immunology · 2026Review
- Pleiotropic effects of GDF-15 to regulate nutritional status: perspectives from body composition to nutrition-related disorders.British journal of biomedical science · 2026Review
- Calcitonin receptor downregulation and exercise-conditioned blood enable systemic muscle stem cell proliferation.Nature communications · 2025Article
- The co-inhibitory receptor TIGIT promotes tissue-protective functions in T cells.Nature immunology · 2025Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
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]).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.