Chronic ethanol consumption decreases murine langerhans cell numbers and delays migration of langerhans cells as well as dermal dendritic cells

Kristin J. Ness, Ji Fan, Werner W. Wilke, Ruth A. Coleman, Robert T. Cook, Annette J. Schlueter

Research output: Contribution to journalArticle

29 Citations (Scopus)

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-α 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.

Original languageEnglish (US)
Pages (from-to)657-668
Number of pages12
JournalAlcoholism: Clinical and Experimental Research
Volume32
Issue number4
DOIs
StatePublished - Apr 2008
Externally publishedYes

Fingerprint

Langerhans Cells
Skin
Ethanol
Cell Count
Fluorescein-5-isothiocyanate
Bone
Irradiation
Transplants
Defects
Flow cytometry
Lymph Nodes
Drinking Water
Chemical activation
Alcohols
Adaptive Immunity
Alcoholics
Epidermis
Dendritic Cells
Cell Movement
Fluorescent Antibody Technique

Keywords

  • Dermal Dendritic Cells
  • Langerhans Cells
  • Migration
  • Mouse
  • Skin

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology

Cite this

Chronic ethanol consumption decreases murine langerhans cell numbers and delays migration of langerhans cells as well as dermal dendritic cells. / Ness, Kristin J.; Fan, Ji; Wilke, Werner W.; Coleman, Ruth A.; Cook, Robert T.; Schlueter, Annette J.

In: Alcoholism: Clinical and Experimental Research, Vol. 32, No. 4, 04.2008, p. 657-668.

Research output: Contribution to journalArticle

Ness, Kristin J. ; Fan, Ji ; Wilke, Werner W. ; Coleman, Ruth A. ; Cook, Robert T. ; Schlueter, Annette J. / Chronic ethanol consumption decreases murine langerhans cell numbers and delays migration of langerhans cells as well as dermal dendritic cells. In: Alcoholism: Clinical and Experimental Research. 2008 ; Vol. 32, No. 4. pp. 657-668.
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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-α 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.",
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AU - Cook, Robert T.

AU - Schlueter, Annette J.

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