The microbial community exhibits remarkable diversity on topographically distinct skin regions, which may be accompanied by differences in skin immune characteristics. Our aim was to compare the immune milieu of healthy sebaceous gland rich (SGR) and sebaceous gland poor (SGP) skin areas, and to analyze its changes in an inflammatory disease of SGR skin. For this purpose, immunohistochemical, immunocytochemical and quantitative real-time PCR analyses of thymic stromal lymphopoietin (TSLP) and other cytokines, phenotypic immune cell markers and transcription factors were carried out in samples from SGP, SGR skin and from papulopustular rosacea (PPR). TSLP mRNA and protein production was also studied in cultured keratinocytes. In SGR skin, higher TSLP expression, dendritic cell (DC) appearance without prominent activation and T cell presence with interleukin (IL)-17/IL-10 cytokine milieu were detected compared to SGP skin. Linoleic acid, a major sebum component, was found to induce TSLP expression dose-dependently in keratinocytes. In PPR, significantly decreased TSLP level and influx of inflammatory DCs and T cells with IL-17/interferon-γ cytokine milieu were observed. According to our results, SGR skin is characterized by a distinct, non-inflammatory immune surveillance, which may explain the preferred localization of inflammatory skin diseases, and can influence future barrier repair therapeutic concepts.3