title: Establishing a Role for Interleukin-17 in Atopic Dermatitis-Related Skin Inflammation.
abstract: BACKGROUND
  Although CD4+T cells are known to contribute to the pathology of atopic dermatitis (AD), the role of T helper 17 cells and interleukin (IL)-17 in skin inflammation remains poorly understood. The aim of this study was to characterize the role of IL-17 in AD-related inflammation and immunopathology.
  
  
  METHODS
  Blood samples were collected from 87 children with AD and 60 healthy control subjects. In addition, 10 skin biopsies from each group were collected. Skin and serum expression levels of IL-17 were analyzed by immunohistochemistry and enzyme-linked immunosorbent assay, respectively. 2,4-Dinitrochlorobenzene (DNCB)-sensitized IL-17 knockout and wild-type mice were used as an animal model of skin AD. The messenger ribonucleic acid expression levels of T helper types 1 and 2 cytokines isolated from mouse skin biopsies were determined by quantitative polymerase chain reaction. Cytokine expression profiles of concanavalin A-stimulated splenocytes and IL-17-treated HaCaT keratinocytes were determined.
  
  
  RESULTS
  IL-17 expression levels were significantly elevated in the skin, but not in the serum, of patients with AD compared with healthy control subjects. Compared with control subjects, skin lesions from AD animal models exhibited significantly reduced epidermal and dermal thicknesses, as well as reduced messenger ribonucleic acid expression levels of T helper type 2 cytokines IL-4 and IL-13. Concanavalin A-stimulated splenocytes isolated from DNCB-treated IL-17 knockout mice showed significantly less production of IL-4 and IL-5 compared with wild-type controls. IL-6 and IL-8 production by IL-17-stimulated HaCaT cells was blocked by inhibitors of p38 kinase and extracellular signal-regulated kinase.
  
  
  CONCLUSIONS
  IL-17 may mediate AD-related immune dysregulation by amplifying the inflammatory response.
authors.affiliation: 1 Department of Dermatology, Children's Hospital of Chong Qing Medical University, Chong Qing, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Tan
authors.affiliation: 2 Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chong Qing, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Yang
authors.affiliation: 3 Department of Respiratory Medicine, Children's Hospital of Chong Qing Medical University, Chong Qing, China.
authors.forename: En-Mei
authors.initials: EM
authors.lastname: Liu
authors.affiliation: 1 Department of Dermatology, Children's Hospital of Chong Qing Medical University, Chong Qing, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D003876:Dermatitis, Atopic / Q000453:epidemiology / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006801:Humans; D007223:Infant; D007249:Inflammation / Q000276:immunology / Q000378:metabolism*; D020381:Interleukin-17 / Q000032:analysis*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction; D012867:Skin / Q000737:chemistry / Q000276:immunology
chemical_list: D020381:Interleukin-17
keywords: atopic dermatitis; inflammation; interleukin-17; skin