title: No impairment of monocyte-derived Langerhans cell phenotype or function in early-onset psoriasis.
abstract: BACKGROUND
  Migration of epidermal Langerhans cells (LCs) in response to the cytokines interleukin (IL)-1β and tumour necrosis factor (TNF)-α is impaired in uninvolved skin of patients with early-onset psoriasis.
  
  
  OBJECTIVE
  To investigate whether this impairment is a reflection of a systemic defect in dendritic cells (DCs), using an established model of monocyte-derived LC-like cells (mLCs).
  
  
  METHODS
  CD14+ monocytes isolated from both patients with psoriasis and healthy control volunteers were cultured in a cytokine cocktail for 5 days to promote their differentiation into mLCs, then stimulated for 24 h with TNF-α, IL-1β (both 100 ng/mL) or medium alone. Cellular surface protein expression was quantified by flow cytometry, and the ability of cells to migrate to media supplemented with C-C motif ligand (CCL)19 was assessed using a Transwell migration assay. The cytokine and chemokine content of supernatants was analysed by cytokine array.
  
  
  RESULTS
  CD14+ cells acquired an LC-like phenotype with high expression of CD1a and major histocompatibility complex (MHC) class II. There were no differences in the expression of activation markers or in the secretion of cytokines by mLCs isolated from patients with psoriasis and those isolated from healthy controls. Moreover, mLCs isolated from both groups displayed comparable ability to migrate in vitro.
  
  
  CONCLUSIONS
  These data suggest that the failure of LCs to migrate in response to stimulation in patients with psoriasis is not attributable to a systemic defect in DC function, but is rather a reflection of local changes in the epidermal microenvironment.
authors.affiliation: Toxicology Group, Faculty of Life Sciences, University of Manchester, Manchester, UK. frances.shaw@manchester.ac.uk
authors.forename: F L
authors.initials: FL
authors.lastname: Shaw
authors.forename: I
authors.initials: I
authors.lastname: Kimber
authors.forename: R
authors.initials: R
authors.lastname: Begum
authors.forename: M
authors.initials: M
authors.lastname: Cumberbatch
authors.forename: R J
authors.initials: RJ
authors.lastname: Dearman
authors.forename: C E M
authors.initials: CE
authors.lastname: Griffiths
mesh_terms: D000293:Adolescent; D000328:Adult; D018949:Antigens, CD1 / Q000276:immunology*; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured / Q000276:immunology; D018925:Chemokines / Q000032:analysis; D016207:Cytokines / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D007801:Langerhans Cells / Q000276:immunology*; D018950:Lipopolysaccharide Receptors; D008285:Major Histocompatibility Complex / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology*; D011565:Psoriasis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D055815:Young Adult
chemical_list: D018949:Antigens, CD1; C419393:CD1a antigen; D018925:Chemokines; D016207:Cytokines; D053583:Interleukin-1beta; D018950:Lipopolysaccharide Receptors; D014409:Tumor Necrosis Factor-alpha