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 tre...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-b-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)-c 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.展开更多
基金the National Institutes of Health(R00AI072956 to YYW)the Beijing Natural Science Foundation(7082054)the National Science and Technology Major Specific Project of the People’s Republic of China(2009ZX09301-010 to WH)and the China Scholarship Council(YGZ).
文摘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-b-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)-c 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.
