先天性淋巴细胞
纤维化
肺
特发性肺纤维化
肺纤维化
医学
病理
获得性免疫系统
炎症
免疫学
免疫系统
内科学
作者
Rana Herro,Haruka Miki,Gurupreet S. Sethi,David Mills,Amit Mehta,Xinh-Xinh Nguyen,Carol Feghali‐Bostwick,Marina Miller,David H. Broide,Rachel Soloff,Michael Croft
出处
期刊:Journal of Immunology
[American Association of Immunologists]
日期:2020-09-21
卷期号:205 (9): 2414-2422
被引量:43
标识
DOI:10.4049/jimmunol.2000665
摘要
Abstract Lung fibrosis and tissue remodeling are features of chronic diseases such as severe asthma, idiopathic pulmonary fibrosis, and systemic sclerosis. However, fibrosis-targeted therapies are currently limited. We demonstrate in mouse models of allergen- and bleomycin-driven airway inflammation that neutralization of the TNF family cytokine TL1A through Ab blocking or genetic deletion of its receptor DR3 restricted increases in peribronchial smooth muscle mass and accumulation of lung collagen, primary features of remodeling. TL1A was found as a soluble molecule in the airways and expressed on the surface of alveolar macrophages, dendritic cells, innate lymphoid type 2 cells, and subpopulations of lung structural cells. DR3 was found on CD4 T cells, innate lymphoid type 2 cells, macrophages, fibroblasts, and some epithelial cells. Suggesting in part a direct activity on lung structural cells, administration of recombinant TL1A into the naive mouse airways drove remodeling in the absence of other inflammatory stimuli, innate lymphoid cells, and adaptive immunity. Correspondingly, human lung fibroblasts and bronchial epithelial cells were found to express DR3 and responded to TL1A by proliferating and/or producing fibrotic molecules such as collagen and periostin. Reagents that disrupt the interaction of TL1A with DR3 then have the potential to prevent deregulated tissue cell activity in lung diseases that involve fibrosis and remodeling.
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