2026-03-05T07:26:38Z https://tokushima-u.repo.nii.ac.jp/oai

oai:tokushima-u.repo.nii.ac.jp:02000206 2025-04-28T06:39:52Z 1713853213384:1713853295607

A Novel DC Therapy with Manipulation of MKK6 Gene on Nickel Allergy in Mice DC Therapy for Ni Allergy in Mice 渡邉, 恵 ワタナベ, メグミ Watanabe, Megumi 渡邉 ワタナベ Watanabe 恵 メグミ Megumi 石丸, 直澄 イシマル, ナオズミ Ishimaru, Naozumi 石丸 イシマル Ishimaru 直澄 ナオズミ Naozumi Ashrin, Meinar Nur 新垣, 理恵子 アラカキ, リエコ Arakaki, Rieko 新垣 アラカキ Arakaki 理恵子 リエコ Rieko 山田, 安希子 ヤマダ, アキコ Yamada, Akiko 山田 ヤマダ Yamada 安希子 アキコ Akiko 市川, 哲雄 イチカワ, テツオ Ichikawa, Tetsuo 市川 イチカワ Ichikawa 哲雄 テツオ Tetsuo 林, 良夫 ハヤシ, ヨシオ Hayashi, Yoshio 林 ハヤシ Hayashi 良夫 ヨシオ Yoshio open access This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background: 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. Methods and Finding: 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. Conclusions: 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. PLOS 2011-04-22 eng journal article VoR 232332 https://tokushima-u.repo.nii.ac.jp/records/2000206 https://doi.org/10.1371/journal.pone.0019017 10.1371/journal.pone.0019017 19326203 PLOS ONE 6 4 e19017 https://tokushima-u.repo.nii.ac.jp/record/2000206/files/pone_6_4_e19017.pdf application/pdf 4 MB 2024-01-01