scholarly journals Commensal Microbiota Regulates Skin Barrier Function And Repair Via Signaling Through The Aryl Hydrocarbon Receptor

2020 ◽  
Author(s):  
Aayushi Uberoi ◽  
Casey Bartow-McKenney ◽  
Qi Zheng ◽  
Laurice Flowers ◽  
Amy Campbell ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Skin Barrier ◽  
The Body ◽  
Epidermal Differentiation ◽  
Skin Barrier Function ◽  
Dependent Manner ◽  
Skin Microbiome ◽  
Barrier Dysfunction ◽  
Epidermal Barrier ◽  
Aryl Hydrocarbon

SUMMARYThe epidermis forms a barrier that defends the body from desiccation and entry of harmful substances, while sensing and integrating environmental signals. The tightly orchestrated cellular changes required for the proper formation and maintenance of this epidermal barrier occur in the context of the skin microbiome. Using germ free mice, we demonstrate the microbiota is necessary for proper differentiation and repair of the epidermal barrier. These effects were mediated by the aryl hydrocarbon receptor (AHR) in keratinocytes, a xenobiotic receptor also implicated in epidermal differentiation. Murine skin lacking keratinocyte AHR was more susceptible to barrier damage and infection, during steady state and epicutaneous sensitization. Colonization with a defined consortium of human skin isolates restored barrier competence in an AHR-dependent manner. We reveal a fundamental mechanism whereby the microbiota regulates skin barrier formation and repair, with far-reaching implications for the numerous skin disorders characterized by epidermal barrier dysfunction.

scholarly journals IL-24 Negatively Regulates Keratinocyte Differentiation Induced by Tapinarof, an Aryl Hydrocarbon Receptor Modulator: Implication in the Treatment of Atopic Dermatitis

2020 ◽  
Vol 21 (24) ◽  
pp. 9412
Author(s):  
Yen Hai Vu ◽  
Akiko Hashimoto-Hachiya ◽  
Masaki Takemura ◽  
Ayako Yumine ◽  
Yasutaka Mitamura ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Aryl Hydrocarbon Receptor ◽  
Skin Barrier ◽  
Janus Kinase ◽  
Keratinocyte Differentiation ◽  
Epidermal Keratinocytes ◽  
Dependent Manner ◽  
Jak Inhibitors ◽  
Barrier Dysfunction ◽  
Aryl Hydrocarbon

Skin barrier dysfunction, including reduced filaggrin (FLG) and loricrin (LOR) expression, plays a critical role in atopic dermatitis (AD) development. Since aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, mediates keratinocyte differentiation, it is a potential target for AD treatment. Recently, clinical studies have shown that tapinarof, an AHR modulator, attenuated the development of AD. To examine the molecular mechanism involved in this, we analyzed tapinarof-treated normal human epidermal keratinocytes (NHEKs). Tapinarof upregulated FLG and LOR mRNA and protein expression in an AHR-dependent manner. Tapinarof also induced the secretion of IL-24, a cytokine that activates Janus kinase (JAK)-signal transducer and activator of transcription (STAT), leading to the downregulation of FLG and LOR expression. Knockdown of either IL-24 or STAT3 expression by small interfering RNA (siRNA) transfection augmented the upregulation of FLG and LOR expression induced by tapinarof, suggesting that inhibition of the IL-24/STAT3 axis during AHR activation supports the improvement of skin barrier dysfunction. Furthermore, tapinarof alone could restore the downregulation of FLG and LOR expression induced by IL-4, a key cytokine of AD, and its combination with JAK inhibitors enhanced this effect. These findings provide a new strategy for treating AD using AHR modulators and JAK inhibitors.

РОЛЬ КОЖНОГО МИКРОБИОЦЕНОЗА В ДИСФУНКЦИИ ЭПИДЕРМАЛЬНОГО БАРЬЕРА И РАЗВИТИИ АТОПИЧЕСКОГО ДЕРМАТИТА У ДЕТЕЙ РАННЕГО ВОЗРАСТА ИЗ ГРУППЫ

2019 ◽  
Author(s):  
N.B. Migacheva
Keyword(s):  
At Risk ◽  
Significant Risk ◽  
Skin Barrier ◽  
Significant Risk Factor ◽  
Transepidermal Water Loss ◽  
Skin Microbiome ◽  
Children At Risk ◽  
Barrier Dysfunction ◽  
Epidermal Barrier

Обоснование. Нарушение кожного микробиоценоза и колонизация кожи S. aureus при атопическом дерматите (АтД) является широко распространенным феноменом и фактором, осложняющим течение заболевания. В настоящее время не вполне понятно, какую роль играет S. aureus в реализации АтД у детей из группы риска по развитию аллергических заболеваний. Цель. Изучение состава кожного микробиоценоза у детей раннего возраста из группы риска, а также роли S. aureus в дисфункции кожного барьера и реализации АтД. Материалы и методы. Проведен анализ 12-месячного наблюдения за 37 детьми из группы риска по развитию аллергических заболеваний, включающий общеклиническое обследование, проведение микробиологического исследования кожи в возрасте 1 и 6 мес и изучение функции эпидермального барьера путем определения показателя трансэпидермальной потери влаги (ТЭПВ) в возрасте 1 3 6 и 12 мес. В качестве исхода рассматривалось формирование АтД в течение периода наблюдения. Результаты. Частота выявления S. aureus на коже детей в возрасте 1 мес составила 45,9, в возрасте 6 мес - 29,7. Корреляционный анализ выявил ассоциацию между колонизацией кожи S. aureus и снижением показателей ТЭПВ (р0,004), а также частотой развития у них АтД (p0,001). Заключение. Обнаружение S. aureus в кожном микробиоценозе детей из группы риска ассоциировано с дисфункцией эпидермального барьера и является значимым фактором риска реализации у них АтД.Background. Colonization of skin with S. aureus in atopic dermatitis (AD) patients is a widespread phenomenon and a factor complicating the course of the disease. At present, it is not quite clear the role of S. aureus in the development of AD in children at risk. The aim of our study was to discribe the skin microbiome composition in young children at risk, as well as to investigate the role of S. aureus in skin barrier dysfunction and the development of AD. Material and methods. 12months follow-up study of 37 infants at risk has been performed. It included a general clinical examination, a microbiological investigation of skin microbiome (at 1 and 6 months), and investigation of epidermal barrier function by determining the transepidermal water loss (TEWL) at 1, 3, 6 and 12 months. Realization of AD during the observation period was considered as main outcome. Results. The prevalence of S. aureus colonization of infants aged 1 month was 45.9, at the age of 6 months - 29.7. Correlation analysis revealed an association between the skin colonization with S. aureus and a decrease of TEWL (p 0.004), as well as the cumulative incidence of AD (p 0.001). Conclusion. The detection of S. aureus as a part of skin microbiocenosis in AD infants at risk is associated with dysfunction of the epidermal barrier and is a significant risk factor for the AD development.

scholarly journals Role of skin microbiome in epidermal barrier dysfunction and development of atopic dermatitis in high risk infants

2019 ◽  
Vol 16 (1) ◽  
pp. 59-64
Author(s):  
N B Migacheva
Keyword(s):  
At Risk ◽  
Atopic Dermatitis ◽  
Skin Barrier ◽  
Transepidermal Water Loss ◽  
Skin Microbiome ◽  
Children At Risk ◽  
Barrier Dysfunction ◽  
Epidermal Barrier ◽  
Microbiome Composition

Background. Colonization of skin with S. aureus in atopic dermatitis (AD) patients is a widespread phenomenon and a factor complicating the course of the disease. At present, it is not quite clear the role of S. aureus in the development of AD in children at risk. The aim of our study was to discribe the skin microbiome composition in young children at risk, as well as to investigate the role of S. aureus in skin barrier dysfunction and the development of AD. Material and methods. 12months follow-up study of 37 infants at risk has been performed. It included a general clinical examination, a microbiological investigation of skin microbiome (at 1 and 6 months), and investigation of epidermal barrier function by determining the transepidermal water loss (TEWL) at 1, 3, 6 and 12 months. Realization of AD during the observation period was considered as main outcome. Results. The prevalence of S. aureus colonization of infants aged 1 month was 45.9%, at the age of 6 months - 29.7%. Correlation analysis revealed an association between the skin colonization with S. aureus and a decrease of TEWL (p = 0.004), as well as the cumulative incidence of AD (p

scholarly journals Effects of mineral complex material treatment on 2,4- dinitrochlorobenzene-induced atopic dermatitis like-skin lesions in mice model

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Johny Bajgai ◽  
Jing Xingyu ◽  
Ailyn Fadriquela ◽  
Rahima Begum ◽  
Dong Heui Kim ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Water Loss ◽  
Immunoglobulin E ◽  
Skin Barrier ◽  
Skin Lesions ◽  
Total Serum ◽  
Skin Barrier Function ◽  
Barrier Dysfunction ◽  
Complex Material ◽  
Mineral Complex

Abstract Background Atopic dermatitis (AD) is a chronic allergic inflammatory skin disease characterized by complex pathogenesis including skin barrier dysfunction, immune-redox disturbances, and pruritus. Prolonged topical treatment with medications such as corticosteroids, calcineurin inhibitors, and T-cell inhibitors may have some potential side-effects. To this end, many researchers have explored numerous alternative therapies using natural products and mineral compounds with antioxidant or immunomodulatory effects to minimize toxicity and adverse-effects. In the current study, we investigated the effects of mineral complex material (MCM) treatment on 2, 4-dinitrochlorobenzene (DNCB)-induced AD-like skin lesions in SKH-1 hairless mice. Methods Animals were divided into four groups; normal control (NC), negative control treated with DNCB only (DNCB only), positive control treated with DNCB and tacrolimus ointment (PC) and experimental group treated with DNCB and MCM patch (MCM). Skin inflammation and lesion severity were investigated through analyses of skin parameters (barrier score and strength, moisture and trans-epidermal water loss level), histopathology, immunoglobulin E, and cytokines. In addition, reactive oxygen species (ROS), nitric oxide (NO), glutathione peroxidase (GPx), and catalase (CAT) levels were measured in both serum and skin lysate. Results Our results demonstrates that MCM patch improved the progression of AD-like skin lesions by significantly increasing skin barrier strength and decreasing trans-epidermal water loss. Additionally, dermal administration of MCM patch significantly reduced epidermal thickness, ROS, and NO levels in skin lysate. Furthermore, we found that MCM suppressed the levels of AD-involved (Th1 and Th2) cytokines such as IL-2, IFN-γ, and IL-4 in blood. In addition, the levels of other Th1, and Th2 and inflammatory cytokines such as IL-1β, TNF-α, IL-6, IL-12(p70) and IL-10 were found lowest in the MCM group than in the DNCB only and PC groups. Moreover, we found total serum IgE level significantly increased after DNCB treatment, but decreased in the PC and MCM groups. Conclusion Taken together, our findings suggest that MCM application may have beneficial effects either systemic or regional on DNCB-induced AD lesional skin via regulation of the skin barrier function and immune-redox response.

Gene regulation of filaggrin and other skin barrier proteins via aryl hydrocarbon receptor

2015 ◽  
Vol 80 (2) ◽  
pp. 83-88 ◽  
Author(s):  
Masutaka Furue ◽  
Gaku Tsuji ◽  
Chikage Mitoma ◽  
Takeshi Nakahara ◽  
Takahito Chiba ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Aryl Hydrocarbon Receptor ◽  
Skin Barrier ◽  
Aryl Hydrocarbon

scholarly journals Rab25 Deficiency Perturbs Epidermal Differentiation and Skin Barrier Function in Mice

2019 ◽  
Vol 27 (6) ◽  
pp. 553-561 ◽  
Author(s):  
Haengdueng Jeong ◽  
Kyung-Min Lim ◽  
James R. Goldenring ◽  
Ki Taek Nam
Keyword(s):  
Barrier Function ◽  
Skin Barrier ◽  
Epidermal Differentiation ◽  
Skin Barrier Function
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