Messing Melina, Theret Marine, Hughes Michael R, Wu Jiaqi, Syed Omar Husain, Li Fang Fang, Li Yicong, Rossi Fabio M V, McNagny Kelly M
School of Biomedical Engineering and Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
EMBO Rep. 2025 Mar;26(5):1406-1421. doi: 10.1038/s44319-025-00383-y. Epub 2025 Feb 3.
Immune responses play an integral role in skeletal muscle regeneration. In the genetically inherited muscle disease Duchenne muscular dystrophy (DMD), muscle regeneration is disrupted, leading to chronic inflammation, fibrosis, and early mortality. Previously, it has been suggested that type-2 innate immune cells, particularly eosinophils and their production of IL-4, play an essential role in effective muscle regeneration after acute injury. We here re-investigate the role of eosinophils in skeletal muscle repair using mice deficient in eosinophils (ΔdblGATA), or deficient in IL-4R/IL-13R signaling through STAT6 (Stat6-/-). We show that neither deficiency has an impact on skeletal muscle regeneration in response to acute injury as quantified by fiber size, immune cell infiltration, or muscle-resident stem cell proliferation. We also investigate the role of STAT6 signaling in mdx:Stat6-/- mice, a model of DMD and, again, find that ablation of STAT6 signaling has no effect on the rate or severity of fibrotic scar formation or disease progression. In contrast to previous models, our data suggest a negligible role for eosinophils and STAT6 signaling in skeletal muscle regeneration after acute or chronic injury.
免疫反应在骨骼肌再生中发挥着不可或缺的作用。在遗传性肌肉疾病杜兴氏肌肉营养不良症（DMD）中，肌肉再生受到破坏，导致慢性炎症、纤维化和早期死亡。此前有研究表明，2型固有免疫细胞，特别是嗜酸性粒细胞及其产生的白细胞介素-4（IL-4），在急性损伤后的有效肌肉再生中起着至关重要的作用。我们在此利用嗜酸性粒细胞缺陷小鼠（ΔdblGATA）或通过信号转导和转录激活因子6（STAT6）缺乏IL-4R/IL-13R信号传导的小鼠（Stat6-/-），重新研究嗜酸性粒细胞在骨骼肌修复中的作用。我们发现，无论是哪种缺陷，在通过纤维大小、免疫细胞浸润或肌肉驻留干细胞增殖量化的急性损伤反应中，对骨骼肌再生均无影响。我们还研究了STAT6信号传导在mdx:Stat6-/-小鼠（一种DMD模型）中的作用，同样发现消除STAT6信号传导对纤维化瘢痕形成的速率或严重程度以及疾病进展没有影响。与之前的模型不同，我们的数据表明，嗜酸性粒细胞和STAT6信号传导在急性或慢性损伤后的骨骼肌再生中作用微乎其微。
