Sebaceous Gland-Rich Skin Is Characterized by TSLP Expression and Distinct Immune Surveillance Which Is Disturbed in Rosacea

Abstract

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

Sebum lipids influence macrophage polarization and activation

“…Based on the findings that the lipid composition of sebum is not a steady‐state condition but can be changed, as was observed both in in vitro sebocytes in response to various stimuli, as well as in the sebum of patients with acne where the variations in the quantity and mostly the quality of sebum lipids could significantly affect inflammation by targeting both keratinocytes and sebocytes, we extended our experiments with P. acnes‐ treated macrophages. Our results provided convincing data that macrophages could also be possible targets for the altered sebum production in acne.…”

Rosacea Is Characterized by a Profoundly Diminished Skin Barrier

“…SGR and SGP skin areas have prominently different homeostatic immune and barrier characteristics (Béke et al, 2018;Dajnoki et al, 2017). Whereas SGR skin regions dispose significantly higher AMP levels, noninflammatory Th17(b) and regulatory T-cell counts, and constitutive expression of homeostatic short form thymic stromal lymphopoietin (sfTSLP), SGP skin is characterized by low AMP levels and T-cell counts, without TSLP presence under steadystate (Béke et al, 2018;Dajnoki et al, 2017). These features of the skin seem to be very similar to that of another barrier, namely the gut, where the regional immune-related differences are well known.…”

“…In addition, we compared PPR barrier damage to that of atopic dermatitis (AD), another inflammatory skin disease with a well-described dysfunctional skin barrier. Because different healthy skin regions have unique immune and barrier characteristics, exclusively SGR skin was used as a healthy control for comparison with PPR specimens (Béke et al, 2018;Dajnoki et al, 2017;Jenei et al, 2019).…”

Endocannabinoid Tone Regulates Human Sebocyte Biology

“…Sebaceous glands (SGs) are important players and regulators of human skin homeostasis. In addition to their obvious function, that is, production of lipid-rich sebum, by which they contribute to the cutaneous lipid barrier and thermoregulation, they also play a role in the endocrine and immune systems of the skin and serve as stem cell reservoirs (Dajnoki et al, 2017;Lupi, 2008;Porter, 2001;Tóth et al, 2011;Zouboulis et al, 2008Zouboulis et al, , 2014.…”