title: A novel DC therapy with manipulation of MKK6 gene on nickel allergy in mice.
abstract: 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.
  
  
  RESULTS
  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.
authors.affiliation: Department of Oral Molecular Pathology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Watanabe
authors.forename: Naozumi
authors.initials: N
authors.lastname: Ishimaru
authors.forename: Meinar Nur
authors.initials: MN
authors.lastname: Ashrin
authors.forename: Rieko
authors.initials: R
authors.lastname: Arakaki
authors.forename: Akiko
authors.initials: A
authors.lastname: Yamada
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ichikawa
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hayashi
mesh_terms: D000818:Animals; D015153:Blotting, Western; D005260:Female; D005434:Flow Cytometry; D006967:Hypersensitivity / Q000276:immunology / Q000628:therapy*; D007150:Immunohistochemistry; D007801:Langerhans Cells / Q000378:metabolism* / Q000502:physiology; D048669:MAP Kinase Kinase 6 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009532:Nickel / Q000009:adverse effects / Q000276:immunology*; D034741:RNA, Small Interfering
chemical_list: D034741:RNA, Small Interfering; D009532:Nickel; D048669:MAP Kinase Kinase 6; C482567:Map2k6 protein, mouse