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

These findings suggest that skin barrier function correlates with the severity of skin inflammation and can be equally impaired in patients with FLG mutant- and wild-type AD with severe symptoms. Nevertheless, our results also suggest that patients with FLG mutant-type AD may have a higher risk of allergic sensitization compared with patients with the wild-type.

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Our aim was to assess whether the presence of highly active effector T cells in atopic dermatitis (AD) is associated with changes in the number and/or function of regulatory T cells (Tregs). Flow cytometry was utilised to determine the percentage of CD4+ CD25bright CD127-/low FOXP3+ and skin-homing CLA+ CD4+ CD25bright FOXP3+ Tregs in healthy controls and AD patients. The correlation between disease severity and Treg percentages was estimated. Treg suppressor activity and cell proliferation were measured after T-cell stimulation. Significantly increased percentages of Tregs were found in AD patients compared to healthy individuals, and significant correlation between the frequency of Tregs and disease severity was also detected. The otherwise normal suppressor activity of Tregs decreased in the presence of Staphylococcus enterotoxin B (SEB). In conclusion, the continuous presence of SEB can trigger an acquired functional impairment of Tregs in AD patients and the correlation between the increased frequency of Tregs and disease severity supports their important role in AD pathogenesis.

Purpose Hyper-IgE syndrome (HIES) is a severe primary immunodeficiency, characterized by increased serum IgE levels as well as recurrent infections and atopic dermatitis (AD)-like skin lesions. AD is a chronic inflammatory skin disease with immunologic alterations (Th2-Th22 polarization) and characteristic skin barrier dysfunctions. Our aim was to investigate physicochemical skin barrier alterations and allergic sensitization in STAT3-HIES patients in order to explore whether skin barrier dysfunction can play a role in the eczematoid skin lesions in these patients. Methods In our experiments STAT3 and FLG mutation analyses were performed in STAT3-HIES (n=7) and AD (n=49) patients. Laboratory parameters (LDH and Eos counts), immunologic alterations (Th17 cell counts), allergic sensitization (total and specific IgE levels, skin prick tests, and medical history records), skin barrier changes [transepidermal water loss (TEWL), skin pH], serum and stratum corneum thymic stromal lymphopoietin (TSLP) levels were also examined.Results Impaired Th17 cell numbers, but normal physicochemical barrier functions, as well as serum and stratum corneum TSLP levels, were found in STAT3-HIES, while these parameters were significantly altered in AD patients. Allergic sensitization was detected in nearly all AD patients, while no signs of sensitization occurred in STAT3-HIES. Conclusions Our study demonstrated that the skin barrier functions of STAT3-HIES patients are not damaged and they differ significantly from the altered skin barrier functions of AD patients. A well-functioning physicochemical skin barrier may be one of the explanations on the contradiction between the extremely high total IgE levels and the lack of allergic sensitization in these patients. Our study underlines the importance of skin barrier in the development of allergic sensitization.