The skin microbiome in the first year of life and its association with atopic dermatitis

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Contact allergy in patients with chronic venous leg ulcers

Contact allergy (CA) is prevalent in patients with chronic leg ulcers (CLUs) due to venous stasis1 and may delay wound healing. Exposure to different ointments and wound dressings over time, combined with occlusive bandaging, may predispose to contact sensitization.2 The spectrum of allergens depends on wound care practices.3, 4 Studies on CA in patients with CLUs from Norway are lacking. To determine the occurrence of CA in patients with CLUs, patch testing was performed with the Leg Ulcer Series (LUS) containing 27 chemicals and five additional substances relevant to wound treatment: Caine mix III and V, hydrocortisone, IntraSite gel (propylene glycol 20%, Smith & Nephew), and Brulidine (dibrompropamidine 0.15%, Sanofi‐Aventis) (Table S1). Fifty‐two of the 97 patients were also tested with the European Baseline Series (EBS) (Table S2)

Hypo-osmotic stress drives IL-33 production in human keratinocytes - An epidermal homeostatic response

Although inflammation has traditionally been considered a response to either exogenous pathogen-associated signals or endogenous signals of cell damage, other perturbations of homeostasis, generally referred to as stress, may also induce inflammation. The relationship between stress and inflammation is, however, not well defined. Here, we describe a mechanism of IL-33 induction driven by hypo-osmotic stress in human keratinocytes and also report interesting differences when comparing the responsiveness of other inflammatory mediators. The induction of IL-33 was completely dependent on EGFR and calcium signaling, and inhibition of calcium signaling not only abolished IL-33 induction but also dramatically changed the transcriptional pattern of other cytokines upon hypo-osmotic stress. IL-33 was not secreted but instead showed nuclear sequestration, conceivably acting as a failsafe mechanism whereby it is induced by potential danger but released only upon more extreme homeostatic perturbations that result in cell death. Finally, stress-induced IL-33 was also confirmed in an ex vivo human skin model, translating this mechanism to a potential tissue-relevant signal in the human epidermis. In conclusion, we describe hypo-osmotic stress as an inducer of IL-33 expression, linking cellular stress to nuclear accumulation of a strong proinflammatory cytokine. © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0

Early transcriptional changes after UVB treatment in atopic dermatitis includes inverse regulation of IL‐36γ and IL‐37

Phototherapy with narrow‐band Ultraviolet B (nb‐UVB) is a major therapeutic option in atopic dermatitis (AD), yet knowledge of the early molecular responses to this treatment is lacking. The objective of this study was to map the early transcriptional changes in AD skin in response to nb‐UVB treatment. Adult patients (n = 16) with AD were included in the study and scored with validated scoring tools. AD skin was irradiated with local nb‐UVB on day 0, 2 and 4. Skin biopsies were taken before and after treatment (day 0 and 7) and analysed for genome‐wide modulation of transcription. When examining the early response after three local UVB treatments, gene expression analysis revealed 77 significantly modulated transcripts (30 down‐ and 47 upregulated). Among them were transcripts related to the inflammatory response, melanin synthesis, keratinization and epidermal structure. Interestingly, the pro‐inflammatory cytokine IL‐36γ was reduced after treatment, while the anti‐inflammatory cytokine IL‐37 increased after treatment with nb‐UVB. There was also a modulation of several other mediators involved in inflammation, among them defensins and S100 proteins. This is the first study of early transcriptomic changes in AD skin in response to nb‐UVB. We reveal robust modulation of a small group of inflammatory and anti‐inflammatory targets, including the IL‐1 family members IL36γ and IL‐37, which is evident before any detectable changes in skin morphology or immune cell infiltrates. These findings provide important clues to the molecular mechanisms behind the treatment response and shed light on new potential treatment targets

Shifts in the Skin Microbiota after UVB Treatment in Adult Atopic Dermatitis

<b><i>Background:</i></b> The pathophysiology in atopic dermatitis (AD) is not fully understood, but immune dysfunction, skin barrier defects, and alterations of the skin microbiota are thought to play important roles. AD skin is frequently colonized with <i>Staphylococcus aureus</i> (<i>S. aureus</i>) and microbial diversity on lesional skin (LS) is reduced compared to on healthy skin. Treatment with narrow-band ultraviolet B (nb-UVB) leads to clinical improvement of the eczema and reduced abundance of <i>S. aureus</i>. However, in-depth knowledge of the temporal dynamics of the skin microbiota in AD in response to nb-UVB treatment is lacking and could provide important clues to decipher whether the microbial changes are primary drivers of the disease, or secondary to the inflammatory process. <b><i>Objectives:</i></b> To map the temporal shifts in the microbiota of the skin, nose, and throat in adult AD patients after nb-UVB treatment. <b><i>Methods:</i></b> Skin swabs were taken from lesional AD skin (<i>n</i> = 16) before and after 3 treatments of nb-UVB, and after 6–8 weeks of full-body treatment. We also obtained samples from non-lesional skin (NLS) and from the nose and throat. All samples were characterized by 16S rRNA gene sequencing. <b><i>Results:</i></b> We observed shifts towards higher diversity in the microbiota of lesional AD skin after 6–8 weeks of treatment, while the microbiota of NLS and of the nose/throat remained unchanged. After only 3 treatments with nb-UVB, there were no significant changes in the microbiota. <b><i>Conclusion:</i></b> Nb-UVB induces changes in the skin microbiota towards higher diversity, but the microbiota of the nose and throat are not altered