title: An essential role for TAK1 in the contact hypersensitivity response.
abstract: Contact hypersensitivity (CHS) is a delayed-type hypersensitivity that can be induced by haptens, such as 2,4-dinitrofluorobenzene (DNFB). Innate and adaptive immunities are both important for the development of CHS. To treat CHS-related diseases, such as allergic contact dermatitis, a disease prevalent in industrialized countries, ways of interfering with improper immune function during CHS responses need to be identified. Transforming growth factor-β-activated kinase-1 (TAK1), a member of mitogen-activated protein kinase kinase kinase family, is important for both innate and adaptive immunities. We thus hypothesized that the CHS response could be inhibited by interfering with TAK1 activity. Using a mouse model in which TAK1 deletion can be locally induced, we observed that TAK deficiency led to an impaired CHS response and was associated with defective T-cell expansion, activation and interferon (IFN)-γ production. In addition, we investigated the effect of deleting TAK1 specifically in dendritic cells (DC) on the CHS response. We found that when TAK1 is deficient in DC, the CHS response was abolished and hapten-elicited T-cell responses were defective. Collectively, this study demonstrates an essential role of TAK1 in the induction of CHS and suggests that targeting TAK1 could be a viable approach to treat CHS.
authors.affiliation: Department of Toxicology, School of Public Health, Peking University, Beijing, China.
authors.forename: Yan G
authors.initials: YG
authors.lastname: Zhao
authors.forename: Yunqi
authors.initials: Y
authors.lastname: Wang
authors.forename: Weidong
authors.initials: W
authors.lastname: Hao
authors.forename: Yisong Y
authors.initials: YY
authors.lastname: Wan
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D003877:Dermatitis, Contact / Q000276:immunology* / Q000378:metabolism; D006241:Haptens / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D006241:Haptens; D007371:Interferon-gamma; D020930:MAP Kinase Kinase Kinases; D000099151:MAP Kinase Kinase Kinase 7