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Lower levels of interleukin‐1 β gene expression are associated with impaired Langerhans’ cell migration in aged human skin
Author(s) -
Pilkington Suzanne M.,
Ogden Stephanie,
Eaton Laura H.,
Dearman Rebecca J.,
Kimber Ian,
Griffiths Christopher E. M.
Publication year - 2018
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12810
Subject(s) - human skin , epidermis (zoology) , tumor necrosis factor alpha , skin biopsy , immune system , gene expression , biology , immunology , interleukin , cytokine , interleukin 22 , langerhans cell , innate immune system , medicine , biopsy , gene , biochemistry , genetics , anatomy
Summary 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‐1 β ( IL ‐1 β ) and tumour necrosis factor‐ α ( TNF ‐ α ) are mandatory signals for LC migration and previous studies suggest that IL ‐1 β 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‐1 β treatment restored LC migration in aged epidermis whereas TNF ‐ α was without effect. In uncultured, aged skin IL ‐1 β gene expression was lower compared with young skin; following culture, IL ‐1 β mRNA remained lower in aged skin under control and TNF ‐ α conditions but was elevated after culture with IL ‐1 β . Interleukin‐1 receptor type 2 ( IL 1R2 ) 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 ‐1 β signalling is diminished due to altered expression of IL 1B and decoy receptor gene IL 1R2 .