title: The effect of ageing on phenotype and function of monocyte-derived Langerhans cells.
abstract: BACKGROUND
  With increasing age the immune system shows functional decline. In the skin this is associated with an increased incidence of epidermal malignancies and infections. Epidermal Langerhans cells (LCs) act as sentinels of the immune system, recognizing, processing and presenting antigen and inducing T-cell responses. Previous investigations have demonstrated a reduction in the number of epidermal LCs in elderly subjects. Moreover, the ability of LCs to migrate in response to tumour necrosis factor (TNF)-α, but not interleukin (IL)-1β, is significantly impaired in the elderly.
  
  
  OBJECTIVE
  To characterize further the changes in LC function that are associated with increasing chronological age, we have evaluated age-related changes in the response of monocyte-derived LCs (mLCs) to IL-1β and TNF-α.
  
  
  METHODS
  The phenotype and function of mLCs were compared in six young (≤ 30 years) and six aged (≥ 70 years) healthy individuals using a combination of flow cytometry, cytokine and chemokine array, and a Transwell migration assay.
  
  
  RESULTS
  Monocytes from aged individuals were able to differentiate into LCs. There were no significant differences in expression of activation markers, or in baseline or inducible cytokine secretion, by mLCs derived from aged or young subjects. Furthermore, migration in response to a chemokine ligand, CCL19, was equivalent in both age groups.
  
  
  CONCLUSIONS
  These data demonstrate that changes in LC function in the elderly are not associated with changes in systemic dendritic cell phenotype and function. Conditioning of LCs in situ by the epidermal microenvironment is likely to be more important.
authors.affiliation: Dermatology Centre, Salford Royal NHS Foundation Trust, University of Manchester, Manchester Academic Health Science Centre, Manchester M6 8HD, UK. Stephanie.ogden@manchester.ac.uk
authors.forename: S
authors.initials: S
authors.lastname: Ogden
authors.forename: R J
authors.initials: RJ
authors.lastname: Dearman
authors.forename: I
authors.initials: I
authors.lastname: Kimber
authors.forename: C E M
authors.initials: CE
authors.lastname: Griffiths
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D016922:Cellular Senescence; D016207:Cytokines / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology*; D007801:Langerhans Cells / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D008297:Male; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha