Our skin is not uniform; besides anatomical and physiological differences, the chemical milieu and microbiota also vary among different skin regions. In addition, our research group has identified a distinct immunological milieu, with increased immunological tuning characterizing the sebaceous gland-rich, sebaceous skin regions compared to the gland-poor, dry areas. However, the onset of the development of these immunotopographical differences is currently unknown. We hypothesize that before puberty, our skin is uniform, and region-specific characteristics only emerge during adolescence due to hormonal changes. To prove this, we aimed to investigate topographically different skin areas derived from healthy children and adults. We performed TaqMan low-density array (TLDA) and examined the gene expression levels of several cytokines, TFs, chemokines, AMPs, and transcription factors in the sebaceous (sebaceous gland-rich [SGR)) and dry (gland-poor [GP]) skin regions of healthy children (0-10 years) and adults (18 years and above) (n=8-8). We did not find significant differences in the examined molecules between the skin regions of children, while, in adulthood, both the dry and sebaceous skin regions exhibited increased immune activity, however, this increase was much more pronounced in the sebaceous skin region with significantly higher expression of IL-17 signaling mediators (e.g. IL-17, IL-1β, lipocalin, S100A family members). Since the most prominent differences were found in the components of IL-17 signaling, we also detected and quantified the source of the IL-17 cytokine in these skin specimens by double immunofluorescence staining at the protein level. Our results suggest that the predominant source of IL-17 is non-pathogenic Th17 cells in all sample types, and Th17 cell count is substantially and significantly increased in the sebaceous skin region of adults. Our findings indicate that the differences detectable between different skin regions in adults are not present in the skin of children, and the topographic immunological differences develop after adolescence.