4 years ago

Lower levels of interleukin-1β gene expression are associated with impaired Langerhans’ cell migration in aged human skin

Lower levels of interleukin-1β gene expression are associated with impaired Langerhans’ cell migration in aged human skin
Ian Kimber, Suzanne M. Pilkington, Laura H. Eaton, Christopher E. M. Griffiths, Rebecca J. Dearman, Stephanie Ogden
Langerhans’ cells (LC) play pivotal roles in skin immune responses, linking innate and adaptive immunity. In aged skin there are fewer LC and migration is impaired compared with young skin. These changes may contribute to declining skin immunity in the elderly, including increased skin infections and skin cancer. Interleukin-1β (IL-1β) and tumour necrosis factor-α (TNF-α) are mandatory signals for LC migration and previous studies suggest that IL-1β signalling may be dysregulated in aged skin. Therefore, we sought to explore the mechanisms underlying these phenomena. In skin biopsies of photoprotected young (< 30 years) and aged (> 70 years) human skin ex vivo, we assessed the impact of trauma, and mandatory LC mobilizing signals on LC migration and gene expression. Biopsy-related trauma induced LC migration from young epidermis, whereas in aged skin, migration was greatly reduced. Interleukin-1β treatment restored LC migration in aged epidermis whereas TNF-α was without effect. In uncultured, aged skin IL-1β gene expression was lower compared with young skin; following culture, IL-1βmRNA remained lower in aged skin under control and TNF-α conditions but was elevated after culture with IL-1β. Interleukin-1 receptor type 2 (IL1R2) gene expression was significantly increased in aged, but not young skin, after cytokine treatment. Keratinocyte-derived factors secreted from young and aged primary cells did not restore or inhibit LC migration from aged and young epidermis, respectively. These data suggest that in aged skin, IL-1β signalling is diminished due to altered expression of IL1B and decoy receptor gene IL1R2. Trauma-induced Langerhans’ cell migration is impaired in aged human skin ex vivo, but can be restored by addition of interleukin-1β (IL-1β). This is attributed to an age-associated deficiency of cutaneous IL-1β, and is supported by a reduced level of IL1B gene expression in skin of aged, compared with young individuals.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/imm.12810

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