Immunotopographical Differences of Human Skin

Abstract

The immunological barrier of the healthy skin is considered to be unified on the whole body surface—however, recent indirect findings have challenged this dogma since microbial and chemical milieu (e.g., sebum, sweat, and pH) exhibit remarkable differences on topographically distinct skin areas. Therefore, in the present study, we performed whole transcriptomic and subsequent pathway analyses to assess differences between sebaceous gland rich (SGR) and sebaceous gland poor (SGP) regions. Here, we provide the first evidence that different skin regions exhibit a characteristic innate and adaptive immune and barrier milieu as we could detect significantly increased chemokine (CCL2, 3, 19, 20, 23, 24) and antimicrobial peptide (S100A7, A8, A9, lipocalin, β-defensin-2) expression, altered barrier (keratin 17, 79) functions, and a non-inflammatory Th17/IL-17 dominance in SGR skin compared to SGP. Regarding pro-inflammatory molecules (IL-1α, IL-6, IL-8, IL-33, TNF-α), similarly low levels were detected in both regions. Our data may explain the characteristic topographical localization of some immune-mediated and autoimmune skin disorders and we also propose that the term “healthy skin control sample,” widely used in experimental Dermatology, should only be accepted if researchers carefully specify the exact region of the healthy skin (along with the site of the diseased sample).

Apocrine Gland–Rich Skin Has a Non-Inflammatory IL-17–Related Immune Milieu, that Turns to Inflammatory IL-17–Mediated Disease in Hidradenitis Suppurativa

“…In our previous studies (Beke et al, 2018;Dajnoki et al, 2017), we reported that sebaceous glanderich skin areas, considered as oily skin, similarly to the previously published topographical distinctions of the microbiota and the chemical milieu (Bouslimani et al, 2015;Grice and Segre, 2011), are equipped with a significantly different immune and barrier supply compared to sebaceous gland-poor areas, considered as dry skin. In the present project, we aimed to further analyze whether AGR areas (as analogous to moist skin in previous literature) also develop their characteristic immune and barrier milieu because these skin regions were proven to possess specific microbiota composition, chemical milieu, moisture content, and temperature appreciably different from apocrine gland-poor (AGP) skin (AGP skin biopsies were taken also from dry skin, similarly to previous sebaceous gland-poor biopsies, containing neither apocrine nor sebaceous glands, detailed identification in Supplementary Table S1 online) (Grice and Segre, 2011).…”

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).…”

Microcomedones in non‐lesional acne prone skin New orientations on comedogenesis and its prevention

“…1 Another important character of NLSAP is the 'invisible microcomedone' (IMC), which can be non-invasively visualized by 'stripping-it-out' with cyanoacrylate glue, the so-called cyanoacrylate skin surface stripping (CSSS), 2,3 and more recently in situ by reflectance confocal microscopy. As a sebaceous gland-rich region, NLSAP also exhibits a characteristic, innate and adaptive immune and barrier, milieu.…”

“…As a sebaceous gland-rich region, NLSAP also exhibits a characteristic, innate and adaptive immune and barrier, milieu. 1 Another important character of NLSAP is the 'invisible microcomedone' (IMC), which can be non-invasively visualized by 'stripping-it-out' with cyanoacrylate glue, the so-called cyanoacrylate skin surface stripping (CSSS), 2,3 and more recently in situ by reflectance confocal microscopy. 4,5 The invisible microcomedone is considered as the root of any subsequent clinical lesion, both non-inflammatory and inflammatory.…”