免疫细胞在肺纤维化中的新作用。
Emerging role of immune cells as drivers of pulmonary fibrosis.
机构信息
Institute for Respiratory Health, The University of Western Australia, Nedlands, WA, Australia.
Institute for Respiratory Health, The University of Western Australia, Nedlands, WA, Australia.
出版信息
Pharmacol Ther. 2023 Dec;252:108562. doi: 10.1016/j.pharmthera.2023.108562. Epub 2023 Nov 10.
The pathogenesis of pulmonary fibrosis, including idiopathic pulmonary fibrosis (IPF) and other forms of interstitial lung disease, involves a complex interplay of various factors including host genetics, environmental pollutants, infection, aberrant repair and dysregulated immune responses. Highly variable clinical outcomes of some ILDs, in particular IPF, have made it difficult to identify the precise mechanisms involved in disease pathogenesis and thus the development of a specific cure or treatment to halt and reverse the decline in patient health. With the advent of in-depth molecular diagnostics, it is becoming evident that the pathogenesis of IPF is unlikely to be the same for all patients and therefore will likely require different treatment approaches. Chronic inflammation is a cardinal feature of IPF and is driven by both innate and adaptive immune responses. Inflammatory cells and activated fibroblasts secrete various pro-inflammatory cytokines and chemokines that perpetuate the inflammatory response and contribute to the recruitment and activation of more immune cells and fibroblasts. The balance between pro-inflammatory and regulatory immune cell subsets, as well as the interactions between immune cell types and resident cells within the lung microenvironment, ultimately determines the extent of fibrosis and the potential for resolution. This review examines the role of the innate and adaptive immune responses in pulmonary fibrosis, with an emphasis on IPF. The role of different immune cell types is discussed as well as novel anti-inflammatory and immunotherapy approaches currently in clinical trial or in preclinical development.
肺纤维化的发病机制,包括特发性肺纤维化(IPF)和其他形式的间质性肺疾病,涉及多种因素的复杂相互作用,包括宿主遗传学、环境污染物、感染、异常修复和失调的免疫反应。一些间质性肺病,特别是 IPF 的高度可变的临床结果,使得难以确定疾病发病机制中涉及的确切机制,因此难以开发出特定的治疗方法来阻止和逆转患者健康状况的下降。随着深入的分子诊断技术的出现,很明显,IPF 的发病机制对于所有患者都不可能相同,因此可能需要不同的治疗方法。慢性炎症是 IPF 的一个主要特征,由先天和适应性免疫反应驱动。炎症细胞和激活的成纤维细胞分泌各种促炎细胞因子和趋化因子,使炎症反应持续,并有助于招募和激活更多的免疫细胞和成纤维细胞。促炎和调节性免疫细胞亚群之间的平衡,以及免疫细胞类型与肺微环境中固有细胞之间的相互作用,最终决定了纤维化的程度和潜在的消退可能性。本文综述了先天和适应性免疫反应在肺纤维化中的作用,重点是 IPF。讨论了不同免疫细胞类型的作用以及目前处于临床试验或临床前开发阶段的新型抗炎和免疫治疗方法。