The control of tissue fibrosis by the inflammatory molecule LIGHT (TNF Superfamily member 14).
The control of tissue fibrosis by the inflammatory molecule LIGHT (TNF Superfamily member 14).
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DOI：
10.1016/j.phrs.2015.12.018
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发表时间：
2016-02
影响因子：
9.3
通讯作者：
Croft M
中科院分区：
文献类型：
--
作者：
Herro R;Croft M
TNF超家族成员LIGHT（TNFSF 14）最近已成为旨在阻止组织纤维化的治疗干预的潜在靶点。从这个角度来看，我们讨论了LIGHT如何影响表征纤维化的炎症和重塑步骤，与许多人类疾病相关，如哮喘，特发性肺纤维化，系统性硬化症和特应性皮炎。LIGHT通过TNF受体超家族中的两种受体HVEM（TNFRSF 14）和LTβR（TNFRSF 3）发挥作用，这两种受体在造血和非造血细胞上广泛表达。LIGHT可以调节浸润性T细胞、巨噬细胞和嗜酸性粒细胞，控制它们在炎症组织中的运输或保留、它们的增殖以及它们产生放大纤维化过程的细胞因子的能力。更有趣的是，LIGHT可以作用于结构细胞，即上皮细胞、成纤维细胞、平滑肌细胞、脂肪细胞和内皮细胞。通过这些细胞上表达的HVEM或LTβR的信号传导，LIGHT可以促进其增殖和趋化因子、生长因子和金属蛋白酶的表达。这将导致上皮细胞、成纤维细胞和平滑肌的增生，细胞外基质蛋白的沉积，血管损伤，以及进一步的免疫改变，其共同构成纤维化。由于其在T细胞中的早期表达，LIGHT可能是纤维化疾病的启动子，但免疫系统中的其他来源也可能意味着LIGHT在维持或维持纤维化活性中的作用。因此，LIGHT可能是一个有吸引力的预后标志物，也是与人类相关的纤维化治疗的一个有吸引力的靶点。光可以影响结构和炎症细胞，以促进纤维化。LIGHT控制促纤维化因子如细胞因子和趋化因子的表达，驱动炎症部位的细胞浸润和活性;诱导细胞外基质蛋白合成和降解;以及参与纤维化的细胞的增殖、生长、分化和增生。漫画设计来自http://www.servier.com。
The TNF Superfamily member LIGHT (TNFSF14) has recently emerged as a potential target for therapeutic interventions aiming to halt tissue fibrosis. In this perspective, we discuss how LIGHT may influence the inflammatory and remodeling steps that characterize fibrosis, relevant for many human diseases presenting with scarring such as Asthma, Idiopathic Pulmonary Fibrosis, Systemic sclerosis, and Atopic Dermatitis. LIGHT acts through two receptors in the TNF receptor superfamily, HVEM (TNFRSF14) and LTβR (TNFRSF3), which are broadly expressed on hematopoietic and non-hematopoietic cells. LIGHT can regulate infiltrating T cells, macrophages, and eosinophils, controlling their trafficking or retention in the inflamed tissue, their proliferation, and their ability to produce cytokines that amplify fibrotic processes. More interestingly, LIGHT can act on structural cells, namely epithelial cells, fibroblasts, smooth muscle cells, adipocytes, and endothelial cells. By signaling through either HVEM or LTβR expressed on these cells, LIGHT can contribute to their proliferation and expression of chemokines, growth factors, and metalloproteinases. This will lead to hyperplasia of epithelial cells, fibroblasts, and smooth muscle, deposition of extracellular matrix proteins, vascular damage, and further immune alterations that in concert constitute fibrosis. Because of its early expression by T cells, LIGHT may be an initiator of fibrotic diseases, but other sources in the immune system could also signify a role for LIGHT in maintaining or perpetuating fibrotic activity. LIGHT may then be an attractive prognostic marker as well as an appealing target for fibrosis therapies relevant to humans. LIGHT can influence both structural and inflammatory cells to promote fibrosis. LIGHT controls the expression of pro-fibrotic factors like cytokines and chemokines driving cellular infiltration and activity in inflamed sites; induction of extracellular matrix protein synthesis and degradation; as well as proliferation, growth, differentiation and hyperplasia of cells involved in fibrosis. Cartoons designed from http://www.servier.com.