Differential Effects of Myeloid Cell PPARδ and IL-10 in Regulating Macrophage Recruitment, Phenotype, and Regeneration following Acute Muscle Injury

2020/08/19 by Steven S. Welc, Steven S Welc, Michelle Wehling-Henricks +7 · 24 citations
Biochemistry, Genetics and Molecular Biology · Immunology and Microbiology · Medicine · #Biology #CD163 #Cell biology #Gene #Genetics #Immune cells in cancer #Immunology #In vitro #In vivo #Inflammation #Knee injuries and reconstruction techniques #Macrophage #Muscle Physiology and Disorders #Myeloid #Phenotype #Proinflammatory cytokine

paper · pdf · doi:10.4049/jimmunol.2000247

published in The Journal of Immunology 205(6), 1664-1677 (American Association of Immunologists)

openalex publication_date 2020/08/19 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/06

Abstract

Abstract Changes in macrophage phenotype in injured muscle profoundly influence regeneration. In particular, the shift of macrophages from a proinflammatory (M1 biased) phenotype to a proregenerative (M2 biased) phenotype characterized by expression of CD206 and CD163 is essential for normal repair. According to the current canonical mechanism regulating for M1/M2 phenotype transition, signaling through PPARδ is necessary for obtaining the M2-biased phenotype. Our findings confirm that the murine myeloid cell–targeted deletion of Ppard reduces expression in vitro of genes that are activated in M2-biased macrophages; however, the mutation in mice in vivo increased numbers of CD206+ M2-biased macrophages and did not reduce the expression of phenotypic markers of M2-biased macrophages in regenerating muscle. Nevertheless, the mutation impaired CCL2-mediated chemotaxis of macrophages and slowed revascularization of injured muscle. In contrast, null mutation of IL-10 diminished M2-biased macrophages but produced no defects in muscle revascularization. Our results provide two significant findings. First, they illustrate that mechanisms that regulate macrophage phenotype transitions in vitro are not always predictive of mechanisms that are most important in vivo. Second, they show that mechanisms that regulate macrophage phenotype transitions differ in different in vivo environments.

Citations

• The MIQE Guidelines: Minimum Information for Publication of Quantitative Real-Time PCR Experiments

Cited by

• Aging of the immune system and impaired muscle regeneration: A failure of immunomodulation of adult myogenesis. [europepmc]
• Does the Interaction between Local and Systemic Inflammation Provide a Link from Psychology and Lifestyle to Tissue Health in Musculoskeletal Conditions? [europepmc]
• Metformin and leucine increase satellite cells and collagen remodeling during disuse and recovery in aged muscle. [europepmc]
• A growth factor-expressing macrophage subpopulation orchestrates regenerative inflammation via GDF-15. [europepmc]
• Xenogeneic skin transplantation promotes angiogenesis and tissue regeneration through activated Trem2 + macrophages. [europepmc]
• Neuroinflammation and Scarring After Spinal Cord Injury: Therapeutic Roles of MSCs on Inflammation and Glial Scar. [europepmc]
• Peripheral Blood-Derived Mesenchymal Stem Cells Modulate Macrophage Plasticity through the IL-10/STAT3 Pathway. [europepmc]
• Macrophage immunomodulation accelerates skeletal muscle functional recovery in aged mice following disuse atrophy. [europepmc]
• Fibrin and Marine-Derived Agaroses for the Generation of Human Bioartificial Tissues: An Ex Vivo and In Vivo Study. [europepmc]
• Intramuscular IL-10 Administration Enhances the Activity of Myogenic Precursor Cells and Improves Motor Function in ALS Mouse Model. [europepmc]
• Treadmill training does not enhance skeletal muscle recovery following disuse atrophy in older male mice. [europepmc]
• Methylsulfonylmethane (MSM) Supplementation in Adult Horses Supports Improved Skeletal Muscle Inflammatory Gene Expression Following Exercise. [europepmc]
• Electrospun Silk Fibroin-Silk Sericin Scaffolds Induced Macrophage Polarization and Vascularization for Volumetric Muscle Loss Injury. [europepmc]
• The Role of Mitochondria in Mediation of Skeletal Muscle Repair. [europepmc]
• Chronic inflammation as a driving factor for sarcopenia: an update on pathophysiology and future therapeutic targets. [europepmc]

Related

• From skeletal muscle damage and regeneration to the hypertrophy induced by exercise: what is the role of different macrophage subsets?
• Differentially Activated Macrophages Orchestrate Myogenic Precursor Cell Fate During Human Skeletal Muscle Regeneration
• Highly Dynamic Transcriptional Signature of Distinct Macrophage Subsets during Sterile Inflammation, Resolution, and Tissue Repair
• Macrophage and fibro-adipogenic progenitor communication in skeletal muscle regeneration: tissue homeostasis and pathogenic remodeling
• Allogeneic adipose-derived stem cells promote ischemic muscle repair by inducing M2 macrophage polarization via the HIF-1α/IL-10 pathway