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Background Sex hormone changes during menopausal transition contribute to declining skin health. However, how menopause and its treatment by hormone replacement therapy (HRT) impact the skin barrier and immune system is unclear. Objectives To examine how menopause and HRT affect the skin barrier and immune cell composition in postmenopausal women following irritant challenge. Methods Two cohorts of postmenopausal women were recruited to the study. The first cohort consisted of 10 untreated women [HRT–; mean (SEM) age 56.5 (1.6) years (range 48–63)] and the second was composed of 8 women receiving HRT [HRT+; mean (SEM) age 54.0 (2.1) years (range 48–63)]. Skin irritation was induced by applying topical sodium lauryl sulfate (SLS) 1.25% to occluded buttock skin for 48 h. Clinical assessment was conducted after 24 h, followed by biopsy of both SLS-challenged and unchallenged skin for analysis of skin barrier proteins and immune cell distribution using immunofluorescence. Results Clinically, there were no significant differences in skin irritant responses between those taking or not taking HRT (including increased skin redness and blood flow). In response to SLS challenge a significant increase in transepidermal water loss (P < 0.05), filaggrin deposition and cytokeratin 10 (K10)+ cell layers (P < 0.01) was observed in individuals receiving HRT compared with the HRT– group. Following SLS challenge in individuals taking HRT, a significant (P < 0.01) reduction in CD207+ cells in the epidermis was observed, accompanied by an increase of CD207+ cells in the dermis, indicative of migrating Langerhans cells (LCs). Significantly fewer migrating LCs were found in those who were not receiving HRT (P < 0.01). Furthermore, the numbers of dermal dendritic cells (DCs), macrophages, and CD11c+CD206– and CD68+CD206– subsets were found to be significantly (P < 0.05) higher in those taking HRT following SLS challenge. Conclusions Individuals receiving HRT displayed enhanced skin barrier response to SLS challenge with thicker filaggrin and increased K10+ epidermal cell layers. Following challenge, HRT users exhibited elevated LC, inflammatory DC and macrophage counts in the dermis. These may render skin both more prone to inflammation and more capable of resolving it, while also promoting skin repair. [ABSTRACT FROM AUTHOR]

Objectives: Solar ultraviolet radiation (UVR) has major adverse effects on human health. While the mechanisms responsible for induction of UVR‐induced inflammation are well‐documented, the mediation of its resolution and longer‐term adaptive homeostasis is unknown. Therefore, we examined the skin immune and lipid profile over time following UVR inflammation. Methods: To investigate the self‐resolving events of UVR inflammation in vivo, human skin was exposed to a single pro‐inflammatory dose of UVR. Skin biopsies and suction blister fluid were taken at intervals up to 2 weeks post‐UVR. The immune infiltrate was quantified by immunohistochemistry, and lipid mediators were profiled by liquid chromatography/mass spectrometry. Results: We identified that cellular resolution events including switching of macrophage phenotype apply to human sunburn. However, UVR‐induced inflammation in humans involves a post‐resolution phase that differs from other experimental models. We demonstrate that 2 weeks after the initiating UVR stimulus, there is considerable immune activity with CD8+GATA3+ T cells maintained in human skin. Our results challenge the dogma of CD4+FOXP3+ T cells being the main effector CD4+ T‐cell population following UVR, with CD4+GATA3+ T cells the dominant phenotype. Furthermore, lipid mediators are elevated 14 days post‐UVR, demonstrating the skin lipid microenvironment does not revert to the tissue setting occurring prior to UVR exposure. Conclusion: We have identified for the first time that CD4+GATA3+ and CD8+GATA3+ T‐cell subpopulations are recruited to UVR‐inflamed human skin, demonstrating discrepancies between the adaptive UVR response in mice and humans. Future strategies to abrogate UVR effects may target these T‐cell subpopulations and also the persistent alteration of the lipid microenvironment post‐UVR. [ABSTRACT FROM AUTHOR]

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 ( 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-1 β signalling is diminished due to altered expression of IL1B and decoy receptor gene IL1R2. [ABSTRACT FROM AUTHOR]

Langerhans cells ( LCs) are sentinels of skin's immune system, their loss from epidermis contributing to UVR suppression of cell-mediated immunity ( CMI). Omega-3 polyunsaturated fatty acids show potential to reduce UVR suppression of CMI in mice and humans, potentially through modulation of LC migration. Our objectives were to examine whether eicosapentaenoic acid ( EPA) ingestion influences UV-mediated effects on epidermal LC numbers and levels of immunomodulatory mediators including prostaglandin ( PG)D2, which is expressed by LC. In a double-blind randomised controlled study, healthy individuals took 5-g EPA-rich (n=40) or control (n=33) lipid for 12 weeks; UVR-exposed and unexposed skin samples were taken pre- and postsupplementation. Epidermal LC numbers were assessed by immunofluorescence for CD1a, and skin blister fluid PG and cytokines were quantified by LC- MS/ MS and Luminex assay, respectively. Presupplementation, UVR reduced mean ( SEM) LC number/mm2 from 913 (28) to 322 (40) ( P<.001), and mean PGD2 level by 37% from 8.1 (11.6) to 5.1 (5.6) pg/μL; P<.001), while IL-8 level increased ( P<.001). Despite confirmation of EPA bioavailability in red blood cells and skin in the active group, no between-group effect of EPA was found on UVR modulation of LC numbers, PGD2 or cytokine levels postsupplementation. Thus, no evidence was found for EPA reduction of photoimmunosuppression through an impact on epidermal LC numbers. Intriguingly, UVR exposure substantially reduced cutaneous PGD2 levels in humans, starkly contrasting with reported effects of UVR on other skin PG. Lowered PGD2 levels could reflect LC loss from the epidermis and/or altered dendritic cell activity and may be relevant for phototherapy of skin disease. [ABSTRACT FROM AUTHOR]

The long-chain n-3 PUFA, EPA, is believed to be important for skin health, including roles in the modulation of inflammation and protection from photodamage. FFQ and blood levels are used as non-invasive proxies for assessing skin PUFA levels, but studies examining how well these proxies reflect target organ content are lacking. In seventy-eight healthy women (mean age 42·8, range 21–60 years) residing in Greater Manchester, we performed a quantitative analysis of long-chain n-3 PUFA nutrition estimated from a self-reported FFQ (n 75) and correlated this with n-3 PUFA concentrations in erythrocytes (n 72) and dermis (n 39). Linear associations between the three n-3 PUFA measurements were assessed by Spearman correlation coefficients and agreement between these measurements was estimated. Average total dietary content of the principal long-chain n-3 PUFA EPA and DHA was 171 (sd 168) and 236 (sd 248) mg/d, respectively. EPA showed significant correlations between FFQ assessments and both erythrocyte (r 0·57, P< 0·0001) and dermal (r 0·33, P= 0·05) levels, as well as between erythrocytes and dermis (r 0·45, P= 0·008). FFQ intake of DHA and the sum of n-3 PUFA also correlated well with erythrocyte concentrations (r 0·50, P< 0·0001; r 0·27, P= 0·03). Agreement between ranked thirds of dietary intake, blood and dermis approached 50 % for EPA and DHA, though gross misclassification was lower for EPA. Thus, FFQ estimates and circulating levels of the dietary long-chain n-3 PUFA, EPA, may be utilised as well-correlated measures of its dermal bioavailability. [ABSTRACT FROM PUBLISHER]

The article discusses research about the role of cyclooxygenase (COX) inhibitors in increasing chemoattractant 12-hydroxyeicosatetraenoic acid in human sunburn. Topics mentioned include the reduction of vasodilator prostaglandin (PG)E2 by COX inhibitors, the assessment of the effect of topical indomethacin on the ultraviolet radiation-induced inflammatory cell infiltrate, and dermal T-lymphocyte infiltration.