title: Chronic ethanol consumption decreases murine Langerhans cell numbers and delays migration of Langerhans cells as well as dermal dendritic cells.
abstract: BACKGROUND
  Chronic alcoholics experience increased incidence and severity of infections, the mechanism of which is incompletely understood. Dendritic cells (DC) migrate from peripheral locations to lymph nodes (LN) to initiate adaptive immunity against infection. Little is known about how chronic alcohol exposure affects skin DC numbers or migration.
  
  
  METHODS
  Mice received 20% EtOH in the drinking water for up to 35 weeks. Baseline Langerhans cell (LC) and dermal DC (dDC) numbers were enumerated by immunofluorescence (IF). LC repopulation after inflammation was determined following congenic bone marrow (BM) transplant and ultraviolet (UV) irradiation. Net LC loss from epidermis was determined by IF following TNF-alpha or CpG stimulation. LC and dDC migration into LN was assessed by flow cytometry following epicutaneous FITC administration.
  
  
  RESULTS
  Chronic EtOH consumption caused a baseline reduction in LC but not dDC numbers. The deficit was not corrected following transplantation with non-EtOH-exposed BM and UV irradiation, supporting the hypothesis that the defect is intrinsic to the skin environment rather than LC precursors. Net loss of LC from epidermis following inflammation was greatly reduced in EtOH-fed mice versus controls. Ethanol consumption for at least 4 weeks led to delayed LC migration into LN, and consumption for at least 8 weeks led to delayed dDC migration into LN following epicutaneous FITC application.
  
  
  CONCLUSIONS
  Chronic EtOH consumption causes decreased density of epidermal LC, which likely results in decreased epidermal immunosurveillance. It also results in altered migratory responsiveness and delayed LC and dDC migration into LN, which likely delays activation of adaptive immunity. Decreased LC density at baseline appears to be the result of an alteration in the skin environment rather than an intrinsic LC defect. These findings provide novel mechanisms to at least partially explain why chronic alcoholics are more susceptible to infections, especially those following skin penetration.
authors.affiliation: Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.
authors.forename: Kristin J
authors.initials: KJ
authors.lastname: Ness
authors.forename: Ji
authors.initials: J
authors.lastname: Fan
authors.forename: Werner W
authors.initials: WW
authors.lastname: Wilke
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Coleman
authors.forename: Robert T
authors.initials: RT
authors.lastname: Cook
authors.forename: Annette J
authors.initials: AJ
authors.lastname: Schlueter
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects / Q000276:immunology; D000818:Animals; D002465:Cell Movement / Q000187:drug effects* / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects*; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D007801:Langerhans Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D012867:Skin / Q000166:cytology / Q000187:drug effects* / Q000276:immunology
chemical_list: D000431:Ethanol