Cytokine concentration across the stratum corneum in atopic dermatitis and healthy controls

AbstractTape stripping is a promising technique for assessment of epidermal biomarkers in inflammatory skin diseases. However, to facilitate its implementation in the clinical practice, a thorough validation regarding sampling strategy is needed. Knowledge of biomarkers variation in concentration across stratum corneum is scarce. Therefore, this study aimed to assess the variability of cytokines across stratum corneum using tape stripping technique by consecutive application of 21 adhesive tapes (D-squame) to lesional and non-lesional skin from 15 patients with atopic dermatitis (AD) and 16 healthy controls. Concentration of cytokines (IL-1α, IL-1b, IL-5, IL-18, IFN-γ, CCL17, CCL22, CCL27, CXCL8, CXCL10, TNF-α, TSLP, VEGFA) was determined in five different depths, using multiplex immunoassay. Comparing tape 4 with tape 21, no cytokine changed significantly in concentration in AD lesional skin. In AD non-lesional skin a small decrease was found for CCL17, CXCL8 and CXCL10. For healthy controls, a decrease was found for IL-1a, IL-1b, VEGFA and an increase for IL-18. Differences were found between AD skin and healthy control skin. Concentration of cytokines was stable across stratum corneum, indicating that sampling of only one tape from the stratum corneum is reliable in reflecting the overall cytokine milieu. Differences between AD and healthy skin confirm robustness of tape stripping for measuring cytokine levels.

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Characterization of Circular RNA Transcriptomes in Psoriasis and Atopic Dermatitis Reveals Disease-specific Expression Profiles

10.1101/2020.05.26.20090019 ◽

2020 ◽

Author(s):

Liviu Ionut Moldovan ◽

Lam Alex Tsoi ◽

Stephen Weidinger ◽

Johann Gudjonsson ◽

Jørgen Kjems ◽

...

Keyword(s):

Atopic Dermatitis ◽

Skin Diseases ◽

Expression Profiles ◽

Circular Rna ◽

Detection Algorithm ◽

Healthy Skin ◽

Inflammatory Skin Diseases ◽

Specific Expression ◽

Lesional Skin ◽

Inflammatory Skin

AbstractBackgroundAtopic dermatitis (AD) and psoriasis, two chronic inflammatory skin diseases, affect a large number of individuals worldwide, and are associated with various comorbidities. Circular RNA (circRNA) constitute a major class of non-coding RNAs that have been implicated in many human diseases, although their potential involvement in inflammatory skin diseases remains elusive.ObjectivesTo compare and contrast the circRNA expression landscapes in paired lesional and non-lesional skin from psoriasis and AD patients relative to skin from unaffected individuals. Moreover, to correlate circRNA expression to disease severity.MethodsWe analyzed high-depth RNA-seq data from paired lesional and non-lesional skin samples from 27 AD patients, 28 psoriasis patients, and 38 healthy controls. CircRNAs and their cognate linear transcripts were quantified using the circRNA detection algorithm, CIRI2.ResultsWe identified 39,286 unique circRNAs in total and found that psoriasis and AD lesional skin could be distinguished from non-lesional and healthy skin based on circRNA expression landscapes. In general, circRNAs were less abundant in lesional relative to non-lesional and healthy skin. Differential expression analyses revealed many significantly downregulated circRNAs, mainly in psoriasis lesional skin, and a strong correlation between psoriasis and AD-related circRNA expression changes was observed. A subset of circRNAs, including ciRS-7, was specifically dysregulated in psoriasis and show promise as biomarkers for discriminating AD from psoriasis.ConclusionPsoriasis and circRNA transcriptomes share expression features, including a global downregulation, but only psoriasis is characterized by several circRNAs being dysregulated independently of their cognate linear transcripts.

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Comparison of Cytokines in Skin Biopsies and Tape Strips from Adults with Atopic Dermatitis

Dermatology ◽

10.1159/000514308 ◽

2021 ◽

pp. 1-6

Author(s):

Stine Simonsen ◽

Peter Brøgger ◽

Sanja Kezic ◽

Jacob P. Thyssen ◽

Lone Skov

Keyword(s):

Atopic Dermatitis ◽

Stratum Corneum ◽

Tape Stripping ◽

Mrna Levels ◽

Protein Levels ◽

Cytokine Levels ◽

Invasive Method ◽

Healthy Control ◽

Skin Biopsies ◽

Control Skin

Skin biomarkers for disease severity and treatment response in atopic dermatitis (AD) are needed. Biopsies cause scarring and tape stripping represents an alternative minimally invasive method for stratum corneum sampling. In this study, we examined the gene expression of cytokines in skin biopsies and cytokines in stratum corneum tape strips collected from adults with AD. We collected punch biopsies and tape strips from healthy controls (<i>n</i> = 6) and subjects with AD (<i>n</i> = 12) at baseline and after 2 weeks of topical treatment with mometasone furoate 0.1% cream. We found that IFN-γ, IL-13, and IL-10 mRNA (biopsies) and IL-1β protein expression levels (tape strips) were significantly increased in lesional AD skin compared to healthy control skin. Treatment with topical corticosteroid led to a significant decrease in mRNA levels for IL-13 and IL-4R but no significant differences in cytokine protein levels measured in tape strips. Finally, we found no significant correlations between cytokine levels in tape strips and mRNA levels in skin biopsies.

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Ubiquitous Overexpression of Chromatin Remodeling Factor SRG3 Exacerbates Atopic Dermatitis in NC/Nga Mice by Enhancing Th2 Immune Responses

International Journal of Molecular Sciences ◽

10.3390/ijms22041553 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1553

Author(s):

Sung Won Lee ◽

Hyun Jung Park ◽

Jungmin Jeon ◽

Yun Hoo Park ◽

Tae-Cheol Kim ◽

...

Keyword(s):

Atopic Dermatitis ◽

Mast Cells ◽

Immune Responses ◽

Chromatin Remodeling ◽

Skin Diseases ◽

Immunoglobulin E ◽

Critical Role ◽

Interleukin 4 ◽

Inflammatory Skin Diseases ◽

Immune Disorder

The SWItch (SWI)3-related gene (SRG3) product, a SWI/Sucrose Non-Fermenting (SNF) chromatin remodeling subunit, plays a critical role in regulating immune responses. We have previously shown that ubiquitous SRG3 overexpression attenuates the progression of Th1/Th17-mediated experimental autoimmune encephalomyelitis. However, it is unclear whether SRG3 overexpression can affect the pathogenesis of inflammatory skin diseases such as atopic dermatitis (AD), a Th2-type immune disorder. Thus, to elucidate the effects of SRG3 overexpression in AD development, we bred NC/Nga (NC) mice with transgenic mice where SRG3 expression is driven by the β-actin promoter (SRG3β-actin mice). We found that SRG3β-actin NC mice exhibit increased AD development (e.g., a higher clinical score, immunoglobulin E (IgE) hyperproduction, and an increased number of infiltrated mast cells and basophils in skin lesions) compared with wild-type NC mice. Moreover, the severity of AD pathogenesis in SRG3β-actin NC mice correlated with expansion of interleukin 4 (IL4)-producing basophils and mast cells, and M2 macrophages. Furthermore, this accelerated AD development is strongly associated with Treg cell suppression. Collectively, our results have identified that modulation of SRG3 function can be applied as one of the options to control AD pathogenesis.

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MCPIP1/Regnase-1 Expression in Keratinocytes of Patients with Hidradenitis Suppurativa: Preliminary Results

International Journal of Molecular Sciences ◽

10.3390/ijms22147241 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7241

Author(s):

Piotr K. Krajewski ◽

Weronika Szukała ◽

Agata Lichawska-Cieślar ◽

Łukasz Matusiak ◽

Jolanta Jura ◽

...

Keyword(s):

Western Blot ◽

Mrna Expression ◽

Hidradenitis Suppurativa ◽

Skin Lesions ◽

Healthy Controls ◽

Lesional Skin ◽

Chemotactic Protein ◽

Healthy Control ◽

Mrna And Protein Expression ◽

Skin Biopsies

The pathogenesis of hidradenitis suppurativa (HS) is yet to be fully understood. However, inflammation is a key element in the development of skin lesions. The aim of this study was to evaluate the expression of monocyte chemotactic protein-1-induced protein-1 (MCPIP1) in the skin of patients suffering from HS. Skin biopsies of 15 patients with HS and 15 healthy controls were obtained and processed for immunohistochemistry, western blot, and real time PCR. The highest mean MCPIP1 mRNA expression was found in the inflammatory lesional skin of HS patients. It was significantly higher than MCPIP1 mRNA expression in the biopsies from both healthy controls and non-lesional skin of HS patients. Western blot analysis indicated that expression of MCPIP1 was elevated within both lesional and non-lesional skin compared to the healthy control. The increased MCPIP1 mRNA and protein expression level in HS lesions may indicate its possible role in the disease pathogenesis.

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Itch in Atopic Dermatitis – What Is New?

Frontiers in Medicine ◽

10.3389/fmed.2021.644760 ◽

2021 ◽

Vol 8 ◽

Author(s):

Franz J. Legat

Keyword(s):

Atopic Dermatitis ◽

Intracellular Signaling ◽

Sleep Disturbances ◽

Skin Diseases ◽

Immunosuppressive Agents ◽

Calcineurin Inhibitors ◽

Inflammatory Skin Diseases ◽

New Era ◽

Short And Long Term ◽

Chronic Pruritus

Atopic dermatitis (AD) is among the most frequent inflammatory skin diseases in humans, affecting up to 20% of children and 10% of adults in higher income countries. Chronic pruritus is a disease-defining symptom of AD, representing the most burdensome symptom for patients. Severe chronic pruritus causes significant sleep disturbances and impaired quality of life, as well as increased anxiety, depression and suicidal behavior. Until recently, skin care, topical corticosteroids, and calcineurin-inhibitors were primarily used to treat mild to moderate AD, while phototherapy and immunosuppressive agents such as corticosteroids, cyclosporine, and methotrexate were used to treat patients with moderate to severe AD. The potential short- and long-term adverse events associated with these treatments or their insufficient therapeutic efficacy limited their use in controlling pruritus and eczema in AD patients over longer periods of time. As our understanding of AD pathophysiology has improved and new systemic and topical treatments have appeared on the market, targeting specific cytokines, receptors, or their intracellular signaling, a new era in atopic dermatitis and pruritus therapy has begun. This review highlights new developments in AD treatment, placing a specific focus on their anti-pruritic effects.

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