Lack of TAK1 in dendritic cells inhibits the contact hypersensitivity response induced by trichloroethylene in local lymph node assay.pdfVIP

Toxicology and Applied Pharmacology 307 (2016) 72–80 Contents lists available at ScienceDirect Toxicology and Applied Pharmacology journal homepage: /locate/ytaap Lack of TAK1 in dendritic cells inhibits the contact hypersensitivity response induced by trichloroethylene in local lymph node assay Pan Yao, Chu Hongqian, Meng Qinghe, Shang Lanqin, Jiang Jianjun, Yang Xiaohua, Wei Xuetao, Hao Weidong ? a Department of Toxicology, School of Public Health, Peking University, Beijing 100191, China b Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing 100191, China article info Article history: Received 23 May 2016 Revised 19 July 2016 Accepted 25 July 2016 Available online 27 July 2016 Keywords: Trichloroethylene Transforming growth factor-β activated kinase1 Dendritic cells Contact hypersensitivity Local lymph node assay abstract Trichloroethylene (TCE) is a ubiquitous environmental contaminant. Occupational TCE exposure has been associated with severe, generalized contact hypersensitivity (CHS) skin disorder. The development of CHS depends on innate and adaptive immune functions. Transforming growth factor-β activated kinase-1 (TAK1) controls the survival of dendritic cells (DCs) that affect the immune system homeostasis. We aimed to investigate the role of TAK1 activity in DC on TCE-induced CHS response. Control mice and DC-speci?c TAK1 deletion mice were treated with 80% (v/v) TCE using local lymph node assay (LLNA) to establish a TCE-induced CHS model. The draining lymph nodes (DLNs) were excised and the lymphocytes were measure for proliferation by BrdUELISA, T-cell phenotype analysis by ?ow cytometry and signaling pathway activation by western blot. The ears were harvested for histopathological analysis. Control mice in the 80% TCE group displayed an in?ammatory response in the ears, increased lymphocyte proliferation, elevated regulatory T-cell and activated T-cell percentages, and more IFN-γ producing CD8+ T cells in DLNs.