Influence of ageing on Langerhans cell migration in mice: identification of a putative deficiency of epidermal interleukin-1beta.
Previous studies in mice have reported a decrease in epidermal Langerhans cell (LC) density in aged skin, however, the impact of this reduction on LC function and cutaneous immune responses is unclear. In the present series of experiments, the frequency of major histocompatibility complex class II+ LC in the epidermis of older (6-month-old) mice was found to be reduced significantly compared with that observed for young (6-8-week-old) mice. LC mobilization and the subsequent accumulation of dendritic cells (DC) in regional lymph nodes in response to topical challenge with a chemical allergen were found to be less vigorous in older mice. Flow cytometric analyses of DC derived from the draining lymph nodes of fluorescein isothiocyanate (FITC)-sensitized mice revealed that the frequency of FITC+-DC arriving in draining lymph nodes was also reduced in older mice but that the fluorescence intensity was comparable. Control and allergen-treated-older mice also displayed decreased total lymph node cellularity. Contact hypersensitivity responses were found not to be compromised in older mice. However, the cytokine regulation of LC migration in the two age groups of mice did differ. LC migration provoked by intradermal injection of tumour necrosis factor-alpha (TNF-alpha) was reduced in older animals, whereas, the percentage of LC that migrated in response to exogenous interleukin-1beta (IL-1beta) was comparable for both young and aged mice. Since both allergen- and TNF-alpha-induced LC responses are known to require receipt by LC of a signal from IL-1beta for effective migration, the suggestion is that impaired LC migration in older mice may be due to a reduced availability of epidermal IL-1beta.
Cumberbatch
Marie
M
Syngenta Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, SK10 4TJ, UK. marie.cumberbatch@syngenta.com
Dearman
Rebecca J
RJ
Kimber
Ian
I
D000375:Aging / Q000502:physiology*; D000485:Allergens / Q000494:pharmacology; D000818:Animals; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology; D003877:Dermatitis, Contact / Q000276:immunology*; D004817:Epidermis / Q000276:immunology*; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1 / Q000172:deficiency*; D007801:Langerhans Cells / Q000166:cytology* / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010081:Oxazolone / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000485:Allergens; D005456:Fluorescent Dyes; D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D010081:Oxazolone; D016650:Fluorescein-5-isothiocyanate