title: Epicutaneous exposure to nickel induces nickel allergy in mice via a MyD88-dependent and interleukin-1-dependent pathway.
abstract: BACKGROUND
  Several attempts to establish a model in mice that reflects nickel allergy in humans have been made. Most models use intradermal injection of nickel in combination with adjuvant to induce nickel allergy. However, such models poorly reflect induction of nickel allergy following long-lasting epicutaneous exposure to nickel.
  
  
  OBJECTIVE
  To develop a mouse model reflecting nickel allergy in humans induced by epicutaneous exposure to nickel, and to investigate the mechanisms involved in such allergic responses.
  
  
  METHODS
  Mice were exposed to NiCl2 on the dorsal side of the ears. Inflammation was evaluated by the swelling and cell infiltration of the ears. T cell responses were determined as numbers of CD4+ and CD8+ T cells in the draining lymph nodes. Localization of nickel was examined by dimethylglyoxime staining.
  
  
  RESULTS
  Epicutaneous exposure to nickel results in prolonged localization of nickel in the epidermis, and induces nickel allergy in mice. The allergic response to nickel following epicutaneous exposure is MyD88-dependent and interleukin (IL)-1 receptor-dependent, but independent of toll-like receptor (TLR)-4.
  
  
  CONCLUSIONS
  This new model for nickel allergy that reflects epicutaneous exposure to nickel in humans shows that nickel allergy is dependent on MyD88 and IL-1 receptor signalling, but independent of TLR4.
authors.affiliation: Department of International Health, Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark.
authors.forename: Marie T
authors.initials: MT
authors.lastname: Vennegaard
authors.forename: Beatrice
authors.initials: B
authors.lastname: Dyring-Andersen
authors.forename: Lone
authors.initials: L
authors.lastname: Skov
authors.forename: Morten M
authors.initials: MM
authors.lastname: Nielsen
authors.forename: Jonas D
authors.initials: JD
authors.lastname: Schmidt
authors.forename: Michael
authors.initials: M
authors.lastname: Bzorek
authors.forename: Steen S
authors.initials: SS
authors.lastname: Poulsen
authors.forename: Allan R
authors.initials: AR
authors.lastname: Thomsen
authors.forename: Anders
authors.initials: A
authors.lastname: Woetmann
authors.forename: Jacob P
authors.initials: JP
authors.lastname: Thyssen
authors.forename: Jeanne D
authors.initials: JD
authors.lastname: Johansen
authors.forename: Niels
authors.initials: N
authors.lastname: Odum
authors.forename: Torkil
authors.initials: T
authors.lastname: Menné
authors.forename: Carsten
authors.initials: C
authors.lastname: Geisler
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Bonefeld
mesh_terms: D000818:Animals; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes; D017449:Dermatitis, Allergic Contact / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D004817:Epidermis / Q000378:metabolism; D005260:Female; D007375:Interleukin-1 / Q000276:immunology* / Q000378:metabolism; D018655:Lymphocyte Count; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology* / Q000378:metabolism; D009532:Nickel / Q000276:immunology* / Q000493:pharmacokinetics; D015398:Signal Transduction
chemical_list: D007375:Interleukin-1; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D009532:Nickel
keywords: IL-1 signalling; MyD88; TLR4; nickel allergy