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

BACKGROUND: 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 Staphylococcus aureus (S. aureus) 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 S. aureus. 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. OBJECTIVES: To map the temporal shifts in the microbiota of the skin, nose, and throat in adult AD patients after nb-UVB treatment. METHODS: Skin swabs were taken from lesional AD skin (n = 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. RESULTS: 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. CONCLUSION: Nb-UVB induces changes in the skin microbiota towards higher diversity, but the microbiota of the nose and throat are not altered.

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.