095 Koebnerisin (S100A15) signals via mTOR in keratinocytes to control epidermal maturation in psoriasis

Abstract

095 Koebnerisin (S100A15) signals via mTOR in keratinocytes to control epidermal maturation in psoriasis C Buerger, S Richert, V Lang, S Diehl, E Hattinger, R Kaufmann and R Wolf 1 Department of Dermatology, Clinic of the Goethe University, Frankfurt, Germany and 2 Department of Dermatology, Ludwig-Maximilian-University, Munich, Germany The mTOR (mechanistic target of rapamycin) pathway is a central regulator of cell growth and differentiation. In psoriasis, the mTOR kinase is activated throughout the whole epidermis, with particularly strong activation in the basal proliferating epidermal layer. To date, diseaseintrinsic factors which regulate epidermal mTOR activity are yet to be investigated. Koebnerisin (S100A15) is an innate anti-microbial and immune-modulatory peptide strongly upregulated in the psoriatic epidermis. Our data revealed that the localization of koebnerisin resembles the activation pattern of the mTOR kinase. We hypothesized a functional link and unveiled that koebnerisin was capable of activating mTOR signaling via the PI3-K/Akt cascade in keratinocytes. Functionally koebnerisin conferred a small effect on keratinocyte proliferation, which emphasizes previous results on the minor role of mTOR signaling in regulating epidermal proliferation. Further, koebnerisin induced mTOR activation interfered with the expression of differentiation markers mostly likely via post-transcriptional regulation. Data suggest a functional link between the innate anti-microbial peptide koebnerisin (S100A15) and mTOR signaling for epidermal maturation and emphasize the mTOR network as a therapeutic target in chronic inflammatory diseases in the skin and beyond. 096 Transcriptomic analysis of epidermal barrier molecules, cytokines and growth factors in atopic dermatitis lesions C Altunbulakli, A Neumann, F Castro Giner, N Garzorz-Stark, M Reiger, M Akdis, C Traidl-Hoffmann and CA Akdis 1 Swiss Institute for Allergy and Asthma Research, University of Zurich, Davos Platz, Switzerland, 2 Experimental Dermato-Immunology, Clinic and Polyclinic for Dermatology and Allergology at Biederstein, Munich, Germany, 3 Functional Genomics Center Zurich, ETH Zurich, Zurich, Switzerland and 4 Chair and Institute of Environmental Medicine, UNIKA-T, Technical University of Munich and Helmholtz Zentrum Munchen e German Research Center for Environmental Health (GmbH), Augsburg, Germany Atopic dermatitis (AD) is one of the most common inflammatory skin diseases in the general population. AD lesions are characterized by defective expression of skin tight junction (TJ) proteins, as well as changes in filaggrin and factors of the immunologic concert. However, regulation of the whole TJ family and cytokine expression during lesion formation remains to be elucidated to understand the key events behind AD lesion formation. Here, we performed RNA-sequencing and transcriptome analysis in punch biopsies from 11 atopic dermatitis patients and 7 healthy controls, comparing gene expression differences between healthy skin, AD lesional skin and AD non-lesional skin samples. Differentially expressed genes between three skin conditions were calculated, hierarchical clustering and principal component analysis of samples were performed, along with enrichment of the involved pathways and correlations between selected gene families. We found significant differential expression between AD patients and healthy donors, and between AD lesional and non-lesional skin samples. Gene expression of the TJ family and its adaptor molecules were downregulated in both AD lesional and non-lesional skin. FLG was found to be downregulated in lesional skin, and Loricrin was found to be downregulated in both lesional and non-lesional AD skin. Novel Inflammatory cytokines IL36A and IL36Gwere observed as upregulated in lesional skin. These results shed light on the functional pathways related to, and possibly leading to, AD formation, elucidating the complex interaction between the TJ system and the immune response.