title: Hyperresponsive TH2 cells with enhanced nuclear factor-kappa B activation induce atopic dermatitis-like skin lesions in Nishiki-nezumi Cinnamon/Nagoya mice.
abstract: BACKGROUND
  Nishiki-nezumi Cinnamon/Nagoya (NC/Nga) mice raised in nonair-controlled conventional circumstances spontaneously develop atopic dermatitis-like skin lesions; however, the underlying mechanisms remain unclear.
  
  
  OBJECTIVE
  We wanted to identify the critical intracellular signaling molecules in T cells that induce atopic dermatitis-like skin legions in NC/Nga mice.
  
  
  METHODS
  We examined the levels of signal transduction and cytokine production in T cells, particularly those in atopic dermatitis-like lesions induced by the topical injection of mite antigens in NC/Nga mice under specific pathogen-free conditions.
  
  
  RESULTS
  In NC/Nga mice maintained under specific pathogen-free conditions, the capability of T(H)1/T(H)2 and T cytotoxic 1/T cytotoxic 2 (Tc1/Tc2) cell differentiation increased significantly. T-cell antigen receptor-mediated activation of the extracellular signal-regulated kinase/mitogen-activated protein kinase cascade and nuclear factor-kappaB (NF-kappaB) signaling were enhanced in NC/Nga T cells. The expression of T(H)2 cytokines (IL-4, IL-13, and IL-5) and that of GATA-binding protein 3 (GATA3), avian musculoaponeurotic fibrosarcoma (c-Maf), NF-kappaB, and activator protein 1 (AP1) selectively increased in draining lymph node T cells of NC/Nga mice. Moreover, the cell transfer of inhibitory NF-kappaB mutant-infected T(H)2 cells reduced ear thickness in the mite antigen-induced skin lesion of NC/Nga mice.
  
  
  CONCLUSIONS
  Hyperresponsive T(H)2 cells with an enhanced activity of NF-kappaB and AP1 play a crucial role in the pathogenesis of atopic dermatitis-like skin lesions in NC/Nga mice.
  
  
  CONCLUSIONS
  These results indicate potential therapeutic usefulness of developing selective inhibitors for NF-kappaB in the treatment of human atopic dermatitis.
authors.affiliation: Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Tenda
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Yamashita
authors.forename: Motoko Y
authors.initials: MY
authors.lastname: Kimura
authors.forename: Akihiro
authors.initials: A
authors.lastname: Hasegawa
authors.forename: Chiori
authors.initials: C
authors.lastname: Shimizu
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kitajima
authors.forename: Atsushi
authors.initials: A
authors.lastname: Onodera
authors.forename: Akane
authors.initials: A
authors.lastname: Suzuki
authors.forename: Nobuo
authors.initials: N
authors.lastname: Seki
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nakayama
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008925:Mites / Q000276:immunology; D016328:NF-kappa B / Q000502:physiology*; D013045:Species Specificity; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism* / Q000637:transplantation
chemical_list: D016207:Cytokines; D016328:NF-kappa B