title: Mite allergen is a danger signal for the skin via activation of inflammasome in keratinocytes.
abstract: BACKGROUND
  Atopic dermatitis (AD) is a chronic inflammatory skin disorder caused by multiple factors. Among them, house dust mite (HDM) allergens are important in the development of AD. In airway allergy, HDM allergens activate innate immunity. However, information regarding the activation of innate immunity by HDM allergens in the skin is limited.
  
  
  OBJECTIVE
  The inflammasome is a key regulator of pathogen recognition and inflammation. We investigated whether HDM allergens activate the inflammasome in epidermal keratinocytes.
  
  
  METHODS
  Keratinocytes were stimulated with Dermatophagoides pteronyssinus, and the activation of caspase-1 and secretion of IL-1β and IL-18 were examined. Formation of the inflammasome was studied by analyzing the subcellular distributions of inflammasome proteins. The importance of specific inflammasome proteins was studied by knocking down their expression through transfection of keratinocytes with lentiviral particles carrying short hairpin RNAs (shRNAs).
  
  
  RESULTS
  D pteronyssinus activated caspase-1 and induced caspase-1-dependent release of IL-1β and IL-18 from keratinocytes. Moreover, D pteronyssinus stimulated assembly of the inflammasome by recruiting apoptosis-associated specklike protein containing a caspase-recruitment domain (ASC), caspase-1, and nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin-domain containing 3 (NLRP3) to the perinuclear region. Finally, infection with lentiviral particles carrying ASC, caspase-1, or NLRP3 shRNAs suppressed the release of IL-1β and IL-18 from the keratinocytes. Activation of the NLRP3 inflammasome by D pteronyssinus was dependent on cysteine protease activity.
  
  
  CONCLUSIONS
  House dust mite allergens are danger signals for the skin. In addition, HDM-induced activation of the NLRP3 inflammasome may play a pivotal role in the pathogenesis of AD.
authors.affiliation: Department of Dermatology, Ehime University Graduate School of Medicine, Ehime, Japan.
authors.forename: Xiuju
authors.initials: X
authors.lastname: Dai
authors.forename: Koji
authors.initials: K
authors.lastname: Sayama
authors.forename: Mikiko
authors.initials: M
authors.lastname: Tohyama
authors.forename: Yuji
authors.initials: Y
authors.lastname: Shirakata
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hanakawa
authors.forename: Sho
authors.initials: S
authors.lastname: Tokumaru
authors.forename: Lujun
authors.initials: L
authors.lastname: Yang
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hirakawa
authors.forename: Koji
authors.initials: K
authors.lastname: Hashimoto
mesh_terms: D000818:Animals; D039741:Antigens, Dermatophagoides / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D040002:Dermatophagoides pteronyssinus / Q000276:immunology; D005455:Fluorescent Antibody Technique; D006801:Humans; D058847:Inflammasomes / Q000187:drug effects*; D053583:Interleukin-1beta / Q000276:immunology; D016209:Interleukin-8 / Q000276:immunology; D015603:Keratinocytes / Q000187:drug effects* / Q000276:immunology; D012867:Skin / Q000187:drug effects* / Q000276:immunology
chemical_list: D039741:Antigens, Dermatophagoides; D058847:Inflammasomes; D053583:Interleukin-1beta; D016209:Interleukin-8