193 Different Skin Regions are Characterized by Distinct Epimmunome Patterns

Abstract

In recent years, we provided the first evidence that in parallel with their distinct microbial and chemical milieu, topographically distinct skin areas show different immune tuning. In the skin, keratinocytes (KCs) produce epimmunomes which molecules can instruct the innate and adaptive immune cells under both homeostatic and inflammatory conditions. In our current study, we aimed to investigate at the molecular level whether epimmunome molecules (IL-25, IL-33, IL-23, IL-8, IL-18, IL-6, IL-24, IL-17C, IL-1α, IL-1β, IL-36, IL-37, IL-38) show different expression levels in distinct healthy skin regions, namely in gland poor (GP), sebaceous gland rich (SGR), and apocrine gland rich (AGR) areas. The expression of epimmunomes were analyzed both at the mRNA and protein levels by RT-qPCR and IHC. According to our results, GP skin is characterized by a pro-Th2 epimmunome milieu with a significantly elevated expression of IL-25, IL-33 at the protein and gene level, while the IL-18, IL-36RA, IL-37 and IL-38 molecules were upregulated at the gene level compared to SGR and AGR regions. On the other hand, both SGR and AGR areas were characterized by a pro-Th17 epimmunome milieu with a significantly higher expression level of IL-17C protein, whereas, in SGR region, IL-1α was upregulated at the protein level while IL-1β and IL-8 at the mRNA level. Our results indicate that distinct skin regions have a unique epimmunome composition even under steady-state. Our findings may further explain why some outside-in skin diseases prefer to be localized to certain skin regions. We propose that the non-inflammatory pro-Th2 immune milieu of GP area predisposes it for the development of Th2-driven atopic dermatitis. On the contrary, the homeostatic pro-Th17 immune milieu makes AGR and SGR areas susceptible for the development of their characteristic Th1/Th17-driven region-specific diseases, hidradenitis suppurativa and rosacea, respectively.