Chikhaoui Asma, Najjar Dorra, Bouchoucha Sami, Boussetta Rim, Achour Nadia Ben, Tizaoui Kalthoum, Kraoua Ichraf, Turki Ilhem, Yacoub-Youssef Houda
Laboratory of Biomedical Genomics and Oncogenetics (LR16IPT05), Institut Pasteur de Tunis, Université Tunis El Manar, El Manar I, Tunis 2092, Tunisia.
Service Orthopédie, Hôpital d'enfant Béchir Hamza, Tunis 1007, Tunisia.
Int J Mol Sci. 2025 Jun 22;26(13):5992. doi: 10.3390/ijms26135992.
Muscle dystrophies are a group of genetic disorders characterized by progressive muscle degeneration. Prednisone is a glucocorticoid drug widely used to prevent muscle weakness in these diseases. Despite its known beneficial role, the effect of intermittent delivery on monocytes' polarization and on dystrophic muscle microenvironment has not yet been thoroughly investigated. In this study, our aim was to identify the phenotype of monocyte subsets in blood and the expression of fibrosis-related genes in dystrophic muscle biopsies in patients receiving intermittent prednisone therapy. We found an increased rate of classical monocytes and a decreased rate of non-classical monocytes that expressed anti-inflammatory marker CD206 in treated patients. In dystrophic muscles, 21 fibrosis-related genes were altered, among which we identified CCAAT/enhancer-binding protein beta . Both classical monocytes and are known for their roles in stimulating collagen 1 production, a probable marker hampering monocyte/macrophage function. Hence, in some patients with muscular dystrophy, intermittent prednisone treatment could shift the monocytes' phenotype toward an M2, senescent-like profile. This seems to decrease the inflammatory infiltrate in muscle tissue, an observation that needs to be further confirmed.
肌肉萎缩症是一组以进行性肌肉退化为特征的遗传性疾病。泼尼松是一种广泛用于预防这些疾病中肌肉无力的糖皮质激素药物。尽管其有益作用已为人所知，但间歇性给药对单核细胞极化和营养不良性肌肉微环境的影响尚未得到充分研究。在本研究中，我们的目的是确定接受间歇性泼尼松治疗的患者血液中单核细胞亚群的表型以及营养不良性肌肉活检中纤维化相关基因的表达。我们发现，接受治疗的患者中，表达抗炎标志物CD206的经典单核细胞比例增加，而非经典单核细胞比例降低。在营养不良性肌肉中，21个纤维化相关基因发生了改变，其中我们鉴定出CCAAT/增强子结合蛋白β。经典单核细胞和都以刺激胶原蛋白1产生而闻名，胶原蛋白1可能是阻碍单核细胞/巨噬细胞功能的标志物。因此，在一些肌肉萎缩症患者中，间歇性泼尼松治疗可能会使单核细胞表型向M2衰老样状态转变。这似乎会减少肌肉组织中的炎性浸润，这一观察结果有待进一步证实。
