title: Lack of TAK1 in dendritic cells inhibits the contact hypersensitivity response induced by trichloroethylene in 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-specific 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 BrdU-ELISA, T-cell phenotype analysis by flow cytometry and signaling pathway activation by western blot. The ears were harvested for histopathological analysis. Control mice in the 80% TCE group displayed an inflammatory 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. In contrast to control mice, DC-specific TAK1 deletion mice in the 80% TCE group showed an abolished CHS response and this was associated with defective T-cell expansion, activation and IFN-γ production. This effect may occur through Jnk and NF-κB signaling pathways. Overall, this study demonstrates a pivotal role of TAK1 in DCs in controlling TCE-induced CHS response and suggests that targeting TAK1 function in DCs may be a viable approach to preventing and treating TCE-related occupational health hazards.
authors.affiliation: Department of Toxicology, School of Public Health, Peking University, Beijing 100191, China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing 100191, China.
authors.forename: Pan
authors.initials: P
authors.lastname: Yao
authors.affiliation: Department of Toxicology, School of Public Health, Peking University, Beijing 100191, China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing 100191, China.
authors.forename: Chu
authors.initials: C
authors.lastname: Hongqian
authors.affiliation: Department of Toxicology, School of Public Health, Peking University, Beijing 100191, China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing 100191, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Qinghe
authors.affiliation: Department of Toxicology, School of Public Health, Peking University, Beijing 100191, China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing 100191, China.
authors.forename: Shang
authors.initials: S
authors.lastname: Lanqin
authors.affiliation: Department of Toxicology, School of Public Health, Peking University, Beijing 100191, China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing 100191, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Jianjun
authors.affiliation: Department of Toxicology, School of Public Health, Peking University, Beijing 100191, China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing 100191, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xiaohua
authors.affiliation: Department of Toxicology, School of Public Health, Peking University, Beijing 100191, China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing 100191, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xuetao
authors.affiliation: Department of Toxicology, School of Public Health, Peking University, Beijing 100191, China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing 100191, China. Electronic address: whao@bjmu.edu.cn.
authors.forename: Hao
authors.initials: H
authors.lastname: Weidong
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000378:metabolism*; D003877:Dermatitis, Contact / Q000235:genetics* / Q000378:metabolism; D005260:Female; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D023441:Local Lymph Node Assay; D020930:MAP Kinase Kinase Kinases / Q000235:genetics*; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D014241:Trichloroethylene; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D048031:JNK Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases; D016328:NF-kappa B; D014241:Trichloroethylene; D048051:p38 Mitogen-Activated Protein Kinases; D000099151:MAP Kinase Kinase Kinase 7
keywords: Contact hypersensitivity; Dendritic cells; Local lymph node assay; Transforming growth factor-β activated kinase-1; Trichloroethylene