Document Detail


An essential role for TAK1 in the contact hypersensitivity response.
MedLine Citation:
PMID:  21552285     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Yan G Zhao; Yunqi Wang; Weidong Hao; Yisong Y Wan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-05-09
Journal Detail:
Title:  Cellular & molecular immunology     Volume:  8     ISSN:  2042-0226     ISO Abbreviation:  Cell. Mol. Immunol.     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-07-04     Completed Date:  2011-12-05     Revised Date:  2012-01-04    
Medline Journal Info:
Nlm Unique ID:  101242872     Medline TA:  Cell Mol Immunol     Country:  China    
Other Details:
Languages:  eng     Pagination:  315-24     Citation Subset:  IM    
Affiliation:
Department of Toxicology, School of Public Health, Peking University, Beijing, China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Dendritic Cells / immunology,  metabolism
Dermatitis, Contact / immunology*,  metabolism
Haptens / immunology,  metabolism
Interferon-gamma / immunology,  metabolism
MAP Kinase Kinase Kinases / immunology*,  metabolism
Mice
Mice, Inbred BALB C
T-Lymphocytes / immunology*,  metabolism
Grant Support
ID/Acronym/Agency:
K99 AI072956-01A1/AI/NIAID NIH HHS; K99 AI072956-02/AI/NIAID NIH HHS; R00 AI072956-03/AI/NIAID NIH HHS; R00 AI072956-04/AI/NIAID NIH HHS; R00AI072956/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Haptens; 82115-62-6/Interferon-gamma; EC 2.7.11.25/MAP Kinase Kinase Kinases; EC 2.7.11.25/MAP kinase kinase kinase 7

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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