243 Permeability and immune barrier differences of healthy human skin

Abstract

Despite the distinct microbial and chemical milieu on topographically distinct skin areas, the immunological and permeability barrier of the healthy skin has been previously considered to be unified on the whole body surface. We provided the first evidence that sebaceous gland rich (SGR) and sebaceous gland poor (SGP) regions exhibit a characteristic innate and adaptive immune milieu (increased chemokine expression and a homeostatic IL-17 dominance in SGR skin). As a next step, we aimed to investigate at the molecular level whether permeability barrier of these regions are also different. We analyzed the expression of the most important barrier structure (FLG, KRT1, 6A, 10, 16, 17, 79, LCE1D, 1F, LOR, SPRR1A, 2A), tight junction and desmosome components (CDSN, CLDN1, 16, 23, CDH1, DSC1, DSG1, OCLN), enzymes related to barrier formation (TGM1, 3, 5, KLK5, 7, 14) and antimicrobial peptides (AMPs; S100A7,8,9, LCN2, hBD2) both at the mRNA and protein levels by RT-qPCR and IHC. Regarding barrier structure molecules and junction components KRT17 and 79 were found to be significantly differentially expressed with higher levels in SGR skin whereas amongst the examined enzymes KLK5 and 7 showed significantly higher levels in SGR at the gene level. Moreover, all investigated AMPs were significantly upregulated in SGR. At the protein level, KRT1, KRT17, S100A8 and LCN2 showed significantly elevated level in SGR skin among the investigated molecules. Similarly to the prominently different immune tuning of SGP and SGR region we could also detect barrier differences between the distinct skin regions which together may explain the characteristic localization of certain immune mediated skin disorders and distinct skin sites may require distinct barrier repair therapies.