Expansion and pathogenic activation of skeletal muscle-resident macrophages in mdx5cv/Ccr2-/- mice

• 成果类型: Article
• 署名作者: Wang, Yinhang; Wang, Xingyu; Alabdullatif, Salam; Homma, Sachiko T.; Alekseyev, Yuriy O.; Zhou, Lan
• 署名单位: Boston University; Boston University; Boston University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-14801
• DOI: 10.1073/pnas.2410095122
• 发表日期: 2025-03-11
• 关键词: duchenne muscular-dystrophy; mdx; monocytes; injury; progenitor; fibrosis; differentiation; regeneration; inflammation; expression

摘要

Infiltrating macrophages contribute to muscle dystrophic changes in Duchenne musblood Ly6Chi inflammatory monocyte recruitment. This is accompanied by transient improvement of muscle damage, fibrosis, and regeneration. The benefit, however, is lost after the expansion of intramuscular Ly6Clo macrophages. To address the mechanisms underlying the Ly6Clo macrophage expansion, we compared mdx5cv/Nur77-/- and mdx5cv/ Ccr2-/-/Nur7-/- mice with mdx5cv and mdx5cv/Ccr2-/- mice, respectively, and found no evidemonstrated the expansion and pathogenic activation of muscle resident macrophages eration, which appeared induced by colony- stimulating factor- 1 (CSF- 1) derived from muscle resident macrophages and supports a regulatory role of FAPs in stimulating the macrophage infiltration is inhibited.