414 Influence of filaggrin genotype on regulatory T cells in atopic dermatitis

Abstract

Genomic approaches to characterize skin bacteria have revealed characteristic site-specificities. In addition, in children with AD, shifts of microbial community structures were described at creases and in particular during flares, which have been postulated to mirror the disturbed skin barrier function and/or cutaneous inflammation at these sites. But it is yet unclear whether they are restricted to predilection sites or a general feature of the skin of AD patients. Further, the impact of distinct abnormalities of epidermal barrier integrity and function such as an inherited filaggrin deficiency and of the acuteness of local inflammation on cutaneous microbial community structures have not been examined so far. The skin microbiome was determined by bacterial 16S rRNA sequencing at 4 different body sites of 10 AD patients and 10 healthy controls matched for age, sex and FLG mutation status. In addition, in AD patients acute and chronic eczema lesions were analysed. Independly from the presence of AD, filaggrin deficiency was associated with decrease of diversity and Proteobacteria abundance. Irrespective of the body site, patients with AD showed an increase of Staphilococci with a predominance of S. epidermidis, which was particularly marked in predilection sites. The cutaneous microbiome at acute and chronic lesions is highly similar independently from the body site. Compared to nonlesional skin, there were gradual shifts in diversity from acute to chronic lesions. S. aureus showed a higher abundance on chronic than on acute lesions. Distinct disturbances of epidermal barrier function such as filaggrin deficiency are associated with shifts of the microbial community composition characterized by a reduced diversity and Proteobacteria abundance. In AD, there is a generalized increase of Staphilococci also on non-predilection sites. The impact of inflammation, i.e. affection by eczema, appears to overlay locoregional influences on microbiome composition. 413Epigenetics modification and autophagy associated to UV radiations on skin models E Caviola VITROSCREEN, Milan, Italy Human aging is characterized by a low-grade systemic inflammation, a condition that has been designated as "inflamm-aging". Mediators of the inflammatory UV-induced response can further be associated and induce genetic and epigenetic changes. UV radiations induce autophagy, a catabolic process that regulate cellular response to UV and directly contribute to the process of photoaging. An experimental model on a human 3D reconstructed skin models has been developed in order to reproduce at molecular and morphological level mechanisms associated to photoaging and inflamm-aging process. The protocol is based on the stress induced by UVA radiation (exposure to 12 J/cm 2) and UVA +UVB (2MED) delivered by Oriel 1KW Xenon, Spectra Physics Lamp (Mod 6271-Xenon 1000 W). The following miR-21, miR -22 and miR -126 belonging to NF-kB signaling and FOXO, SIRT-1, ATR, AMK, TSC1/2, P62, SESN2, UVRAG genes relevant for autophagy process have been quantified by qR...