• Tianwen Lai, Baoping Tian, Chao Cao, Yue Hu, Jiesen Zhou, Yong Wang, Yanping Wu, Zhouyang Li, Xuchen Xu, Min Zhang, Feng Xu, Yuan Cao, Min Chen, Dong Wu, Bin Wu, Chen Dong, Wen Li, Songmin Ying, Zhihua Chen, and Huahao Shen.
• Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China; Department of Respiratory and Critical Care Medicine, Affiliated Hospital, Institute of Respiratory Diseases, Guangdong Medical University, Zhanjiang, China.
• Chest. 2018 Apr 1; 153 (4): 863-875.

BackgroundAlthough airway remodeling is a central feature of COPD, the mechanisms underlying its development have not been fully elucidated. The goal of this study was to determine whether histone deacetylase (HDAC) 2 protects against cigarette smoke (CS)-induced airway remodeling through IL-17A-dependent mechanisms.MethodsSputum samples and lung tissue specimens were obtained from control subjects and patients with COPD. The relationships between HDAC2, IL-17A, and airway remodeling were investigated. The effect of HDAC2 on IL-17A-mediated airway remodeling was assessed by using in vivo models of COPD induced by CS and in vitro culture of human bronchial epithelial cells and primary human fibroblasts exposed to CS extract, IL-17A, or both.ResultsHDAC2 and IL-17A expression in the sputum cells and lung tissue samples of patients with COPD were associated with bronchial wall thickening and collagen deposition. Il-17a deficiency (Il-17a-/-) resulted in attenuation of, whereas Hdac2 deficiency (Hdac2+/-) exacerbated, CS-induced airway remodeling in mice. IL-17A deletion also attenuated airway remodeling in CS-exposed Hdac2+/- mice. HDAC2 regulated IL-17A production partially through modulation of CD4+ T cells during T helper 17 cell differentiation and retinoid-related orphan nuclear receptor γt in airway epithelial cells. In vitro, IL-17A deficiency attenuated CS-induced mouse fibroblast activation from Hdac2+/- mice. IL-17A-induced primary human fibroblast activation was at least partially mediated by autocrine production of transforming growth factor beta 1.ConclusionsThese findings suggest that activation of HDAC2 and/or inhibition of IL-17A production could prevent the development of airway remodeling by suppressing airway inflammation and modulating fibroblast activation in COPD.Copyright © 2017. Published by Elsevier Inc.

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