de Zawadzki Andressa, Leeming Diana J, Sanyal Arun J, Anstee Quentin M, Schattenberg Jörn M, Friedman Scott L, Schuppan Detlef, Karsdal Morten A
Nordic Bioscience A/S, Biomarkers & Research, Herlev, Denmark.
Nordic Bioscience A/S, Biomarkers & Research, Herlev, Denmark.
J Hepatol. 2025 Mar 7. doi: 10.1016/j.jhep.2025.02.039.
Fibrosis is a pathological condition characterised by excessive accumulation of extracellular matrix (ECM) components, particularly collagens, leading to tissue scarring and organ dysfunction. In fibrosis, an imbalance between collagen synthesis (fibrogenesis) and degradation (fibrolysis) results in the deposition of fibrillar collagens disrupting the structural integrity of the ECM and, consequently, tissue architecture. Fibrosis is associated with a wide range of chronic diseases, including cirrhosis, kidney fibrosis, pulmonary fibrosis, and autoimmune diseases. Recently, the concept of "hot" and "cold" fibrosis has emerged, referring to the immune status within fibrotic tissues and the nature of fibrogenic signalling. Hot fibrosis is characterised by active immune cell infiltration and inflammation, while cold fibrosis is associated with auto- and paracrine myofibroblast activation, immune cell exclusion and quiescence. In this article, we explore the relationship between hot and cold fibrosis, the role of various types of collagens and their biologically active fragments in modulating the immune system, and how serological ECM biomarkers can help improve our understanding of the disease-relevant interactions between immune and mesenchymal cells in fibrotic tissues. Additionally, we draw lessons from immuno-oncology research in solid tumours to shed light on potential strategies for fibrosis treatment and highlight the advantage of having a "hot fibrotic environment" to treat fibrosis by enhancing collagen degradation through modulation of the immune system.
纤维化是一种病理状态，其特征在于细胞外基质（ECM）成分过度积累，尤其是胶原蛋白，导致组织瘢痕形成和器官功能障碍。在纤维化过程中，胶原蛋白合成（纤维生成）与降解（纤维溶解）之间的失衡导致纤维状胶原蛋白沉积，破坏了ECM的结构完整性，进而破坏了组织结构。纤维化与多种慢性疾病相关，包括肝硬化、肾纤维化、肺纤维化和自身免疫性疾病。最近，“热”纤维化和“冷”纤维化的概念出现了，这指的是纤维化组织内的免疫状态以及纤维生成信号的性质。热纤维化的特征是活跃的免疫细胞浸润和炎症，而冷纤维化与自分泌和旁分泌肌成纤维细胞活化、免疫细胞排除和静止有关。在本文中，我们探讨了热纤维化和冷纤维化之间的关系、各种类型的胶原蛋白及其生物活性片段在调节免疫系统中的作用，以及血清学ECM生物标志物如何有助于增进我们对纤维化组织中免疫细胞和间充质细胞之间疾病相关相互作用的理解。此外，我们从实体瘤免疫肿瘤学研究中汲取经验教训，以阐明纤维化治疗的潜在策略，并强调通过调节免疫系统增强胶原蛋白降解来治疗纤维化的“热纤维化环境”的优势。
