Neurology Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy.
Stem Cell Laboratory, Dino Ferrari Center, Department of Pathophysiology and Transplantation, University of Milan, 20100 Milan, Italy.
Int J Mol Sci. 2024 Jan 3;25(1):631. doi: 10.3390/ijms25010631.
Mounting evidence underscores the intricate interplay between the immune system and skeletal muscles in Duchenne muscular dystrophy (DMD), as well as during regular muscle regeneration. While immune cell infiltration into skeletal muscles stands out as a prominent feature in the disease pathophysiology, a myriad of secondary defects involving metabolic and inflammatory pathways persist, with the key players yet to be fully elucidated. Steroids, currently the sole effective therapy for delaying onset and symptom control, come with adverse side effects, limiting their widespread use. Preliminary evidence spotlighting the distinctive features of T cell profiling in DMD prompts the immuno-characterization of circulating cells. A molecular analysis of their transcriptome and secretome holds the promise of identifying a subpopulation of cells suitable as disease biomarkers. Furthermore, it provides a gateway to unraveling new pathological pathways and pinpointing potential therapeutic targets. Simultaneously, the last decade has witnessed the emergence of novel approaches. The development and equilibrium of both innate and adaptive immune systems are intricately linked to the gut microbiota. Modulating microbiota-derived metabolites could potentially exacerbate muscle damage through immune system activation. Concurrently, genome sequencing has conferred clinical utility for rare disease diagnosis since innovative methodologies have been deployed to interpret the functional consequences of genomic variations. Despite numerous genes falling short as clinical targets for MD, the exploration of Tdark genes holds promise for unearthing novel and uncharted therapeutic insights. In the quest to expedite the translation of fundamental knowledge into clinical applications, the identification of novel biomarkers and disease targets is paramount. This initiative not only advances our understanding but also paves the way for the design of innovative therapeutic strategies, contributing to enhanced care for individuals grappling with these incapacitating diseases.
越来越多的证据强调了免疫系统和骨骼肌肉在杜氏肌营养不良症 (DMD) 以及在正常肌肉再生过程中的复杂相互作用。虽然免疫细胞浸润到骨骼肌肉是疾病病理生理学中的一个突出特征，但涉及代谢和炎症途径的众多次要缺陷仍然存在，关键参与者尚未完全阐明。类固醇是目前唯一有效的延迟发病和控制症状的治疗方法，但它有不良反应，限制了其广泛应用。初步证据强调了 DMD 中 T 细胞特征分析的独特特征，促使对循环细胞进行免疫特征分析。对其转录组和分泌组进行分子分析有望识别出适合作为疾病生物标志物的细胞亚群。此外，它为揭示新的病理途径和确定潜在的治疗靶点提供了途径。同时，过去十年出现了新的方法。先天和适应性免疫系统的发展和平衡与肠道微生物群密切相关。调节微生物衍生的代谢物可能通过免疫系统激活加剧肌肉损伤。与此同时，基因组测序由于采用了创新性方法来解释基因组变异的功能后果，因此在罕见病诊断方面具有临床应用价值。尽管许多基因未能成为 MD 的临床靶点，但 Tdark 基因的探索有望为发现新的、未知的治疗见解提供可能。在将基础知识快速转化为临床应用的过程中，确定新的生物标志物和疾病靶点至关重要。这一举措不仅增进了我们的理解，还为设计创新的治疗策略铺平了道路，有助于为那些与这些致残性疾病作斗争的个体提供更好的护理。
