Type 2 Immune Mechanisms in Carbon Nanotube-Induced Lung Fibrosis.
Type 2 Immune Mechanisms in Carbon Nanotube-Induced Lung Fibrosis.
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DOI：
10.3389/fimmu.2018.01120
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发表时间：
2018
影响因子：
7.3
通讯作者：
Ma Q
中科院分区：
文献类型：
--
作者：
Dong J;Ma Q
T辅助细胞(Th)2依赖的2型免疫通路已被认为是纤维化发生发展的重要驱动因素。在刺激下，激活的Th2免疫细胞和2型细胞因子与炎症和组织修复功能相互作用，刺激对组织损伤的过度热情修复反应，导致器官纤维化和破坏。在这一点上，类型2通路被各种侮辱和病理条件激活以调节反应。碳纳米管(CNTs)是一种应用广泛的纳米材料。然而，肺暴露于碳纳米管会导致动物肺的一些病理结果，主要是炎症和纤维化。这些发现，加上近年来碳纳米管和含碳纳米管材料的生产和商业化的迅速扩大，引起了人们对人体接触碳纳米管的健康风险的担忧。碳纳米管诱导的肺纤维化病变在一定程度上与特发性肺纤维化、尘肺等人类纤维化肺疾病的病变发展和病理特征相似。在纤维化的情况下，免疫细胞被激活，包括不同的免疫途径，从天生的免疫细胞激活到自身免疫性疾病。这些事件通常在纤维化发生之前和/或伴随发生。在CNT暴露后，可以观察到肺中Th2细胞和2型细胞因子的显著诱导和激活。此外，2型途径通过产生2型促纤维化因子和诱导巨噬细胞对CNT的修复表型，在促进CNT诱导的肺纤维化中发挥重要作用。鉴于对纳米安全需求的大幅增加，以及2型免疫通路在肺纤维化中的明显诱导和多重作用，我们综述了目前关于碳纳米管诱导肺纤维化的文献，重点介绍了碳纳米管诱导和激活2型反应以及2型信号在肺纤维化发展中的刺激作用。这些分析为理解碳纳米管诱导的肺纤维化的机制提供了新的见解，以及将2型反应用作人类纤维化肺疾病的监测目标和治疗策略的可能性。
T helper (Th) 2-dependent type 2 immune pathways have been recognized as an important driver for the development of fibrosis. Upon stimulation, activated Th2 immune cells and type 2 cytokines interact with inflammatory and tissue repair functions to stimulate an overzealous reparative response to tissue damage, leading to organ fibrosis and destruction. In this connection, type 2 pathways are activated by a variety of insults and pathological conditions to modulate the response. Carbon nanotubes (CNTs) are nanomaterials with a wide range of applications. However, pulmonary exposure to CNTs causes a number of pathologic outcomes in animal lungs, dominated by inflammation and fibrosis. These findings, alongside the rapidly expanding production and commercialization of CNTs and CNT-containing materials in recent years, have raised concerns on the health risk of CNT exposure in humans. The CNT-induced pulmonary fibrotic lesions resemble those of human fibrotic lung diseases, such as idiopathic pulmonary fibrosis and pneumoconiosis, to a certain extent with regard to disease development and pathological features. In fibrotic scenarios, immune cells are activated including varying immune pathways, ranging from innate immune cell activation to autoimmune disease. These events often precede and/or accompany the occurrence of fibrosis. Upon CNT exposure, significant induction and activation of Th2 cells and type 2 cytokines in the lungs are observed. Moreover, type 2 pathways are shown to play important roles in promoting CNT-induced lung fibrosis by producing type 2 pro-fibrotic factors and inducing the reparative phenotypes of macrophages in response to CNTs. In light of the vastly increased demand for nanosafety and the apparent induction and multiple roles of type 2 immune pathways in lung fibrosis, we review the current literature on CNT-induced lung fibrosis, with a focus on the induction and activation of type 2 responses by CNTs and the stimulating function of type 2 signaling on pulmonary fibrosis development. These analyses provide new insights into the mechanistic understanding of CNT-induced lung fibrosis, as well as the potential of using type 2 responses as a monitoring target and therapeutic strategy for human fibrotic lung disease.