A novel DC therapy with manipulation of MKK6 gene on nickel allergy in mice.
A novel DC therapy with manipulation of MKK6 gene on nickel allergy in mice.
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DOI：
10.1371/journal.pone.0019017
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发表时间：
2011-04-22
期刊：
影响因子：
3.7
通讯作者：
Hayashi Y
中科院分区：
文献类型：
--
作者：
Watanabe M;Ishimaru N;Ashrin MN;Arakaki R;Yamada A;Ichikawa T;Hayashi Y
虽然通过p38丝裂原活化蛋白激酶（MAPK）激活真皮树突状细胞（DC）或朗格汉斯细胞（LC）在金属过敏的发病机制中起着至关重要的作用，但体内分子机制尚未确定，并且尚未建立使用真皮DC或LC的控制的可能的治疗策略。在这项研究中，我们专注于真皮树突状细胞，以确定在小鼠镍（Ni）过敏模型中的金属过敏发病机制的体内机制。还研究了DC治疗对Ni过敏反应的影响。在该模型中，通过p38 MAPK激活真皮DC触发T细胞介导的过敏性免疫应答。在DC中的MAPK信号级联中，Ni在增加的DC活化后有效地磷酸化MAP激酶激酶6（MKK 6）。镍刺激的DC可引发T细胞活化以诱导镍过敏。有趣的是，当将MKK6基因转染的DC转移到模型小鼠中时，观察到更明显的过敏反应。此外，注射靶向MKK6基因的短干扰（si）RNA保护Ni免疫后的超敏反应。Ni对T细胞的激活和MKK6介导的DC激活之间的协同作用在Ni过敏的发生中起重要作用。镍激活DC在镍过敏的发生中起重要作用。在DC中操纵MKK6基因可能是皮肤镍过敏的良好治疗策略。
Although the activation of dermal dendritic cells (DCs) or Langerhans cells (LCs) via p38 mitogen-activated protein kinase (MAPK) plays a crucial role in the pathogenesis of metal allergy, the in vivo molecular mechanisms have not been identified and a possible therapeutic strategy using the control of dermal DCs or LCs has not been established. In this study, we focused on dermal DCs to define the in vivo mechanisms of metal allergy pathogenesis in a mouse nickel (Ni) allergy model. The effects of DC therapy on Ni allergic responses were also investigated. The activation of dermal DCs via p38 MAPK triggered a T cell-mediated allergic immune response in this model. In the MAPK signaling cascade in DCs, Ni potently phosphorylated MAP kinase kinase 6 (MKK6) following increased DC activation. Ni-stimulated DCs could prime T cell activation to induce Ni allergy. Interestingly, when MKK6 gene-transfected DCs were transferred into the model mice, a more pronounced allergic reaction was observed. In addition, injection of short interfering (si) RNA targeting the MKK6 gene protected against a hypersensitivity reaction after Ni immunization. The cooperative action between T cell activation and MKK6-mediated DC activation by Ni played an important role in the development of Ni allergy. DC activation by Ni played an important role in the development of Ni allergy. Manipulating the MKK6 gene in DCs may be a good therapeutic strategy for dermal Ni allergy.
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DOI：
10.1073/pnas.95.16.9482
发表时间：
1998-08-04
影响因子：
11.1
作者：
Fields, RC;Shimizu, K;Mulé, JJ
通讯作者：
Mulé, JJ
影响因子：
4.4
作者：
Arrighi, JF;Rebsamen, M;Hauser, C
通讯作者：
Hauser, C
影响因子：
6.5
作者：
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通讯作者：
BOS, JD
影响因子：
10.3
作者：
Mortz, CG;Lauritsen, JM;Andersen, KE
通讯作者：
Andersen, KE
影响因子：
20.3
作者：
Joergl, Almut;Platzer, Barbara;Strobl, Herbert
通讯作者：
Strobl, Herbert