Atopic Dermatitis and Type 2 Immune Deviation

Furue, Masutaka; Ulzii, Dugarmaa; Vu, Yen Hai; Tsuji, Gaku; Kido‐Nakahara, Makiko; Nakahara, Takeshi

doi:10.1007/s40521-019-00219-w

Cited by 6 publications

(4 citation statements)

References 97 publications

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“…AD-related cytokines and chemokines, which are expressed and secreted in AD-induced mast cells, can cause acute and chronic AD. The indirect activation of Th2 cells is induced by the activation of eosinophils and mast cells [ 57 ]. In the present study, DAA inhibited the protein secretion and gene expression of IL-1β, IL-6, IL-8, TNF-α, and MCP-1 in HaCaT cells in a concentration-dependent manner ( Figure 5 and Figure 6 ).…”

Section: Discussionmentioning

confidence: 99%

Effects of Deacetylasperulosidic Acid on Atopic Dermatitis through Modulating Immune Balance and Skin Barrier Function in HaCaT, HMC-1, and EOL-1 Cells

Seong

Kim³

et al. 2021

Molecules

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The medicinal plant noni (Morinda citrifolia) is widely dispersed throughout Southeast Asia, the Caribbean, and Australia. We previously reported that fermented Noni could alleviate atopic dermatitis (AD) by recovering Th1/Th2 immune balance and enhancing skin barrier function induced by 2,4-dinitrochlorobenzene. Noni has a high deacetylasperulosidic acid (DAA) content, whose concentration further increased in fermented noni as an iridoid constituent. This study aimed to determine the anti-AD effects and mechanisms of DAA on HaCaT, HMC-1, and EOL-1 cells. DAA inhibited the gene expression and secretion of AD-related cytokines and chemokines including interleukin (IL)-1β, IL-4, IL-6, IL-8, IL-25, IL-33, thymic stromal lymphopoietin, tumor necrosis factor-alpha, monocyte chemoattractant protein-1, thymus and activation-regulated chemokine, macrophage-derived chemokine, and regulated upon activation, normal T cell expressed and secreted, in all cells, and inhibited histamine release in HMC-1 cells. DAA controlled mitogen-activated protein kinase phosphorylation levels and the translocation of nuclear factor-kappa light chain enhancer of activated B cells into the nucleus by inhibiting IκBα decomposition in all the cells. Furthermore, DAA increased the expression of proteins involved in skin barrier functions such as filaggrin and involucrin in HaCaT cells. These results confirmed that DAA could relieve AD by controlling immune balance and recovering skin barrier function.

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Section: Discussionmentioning

confidence: 99%

Effects of Deacetylasperulosidic Acid on Atopic Dermatitis through Modulating Immune Balance and Skin Barrier Function in HaCaT, HMC-1, and EOL-1 Cells

Seong

Kim³

et al. 2021

Molecules

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“…Given that Th2 cells are intimately linked with the acute phase of AD, 36 we first aimed to polarize autologous human PBMC‐derived T cells isolated from healthy, non‐atopic donors in vitro towards a mixture of T cells that prominently included CD4+ and Tc2 cells with a Th2 phenotype 10 by exposing them to different combinations of IL‐4, 16 IL‐2, 17,18 and LPS. FACS analysis demonstrated that the majority of T cells (CD3 + ) from PBMCs cultured for 2 weeks without cytokines or only with IL‐4 failed to express the hallmark Th2 transcription factor GATA3 37,38 (Figure S1A,B).…”

Section: Resultsmentioning

confidence: 99%

Autologous Th2‐polarized lymphocytes induce atopic dermatitis lesions in non‐atopic human skin xenotransplants

Keren

Reich

Bertolini

et al. 2023

Allergy

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Background:The key signals that suffice to induce atopic dermatitis (AD) in human skin remain incompletely understood. Also, current mouse models reflect human AD only unsatisfactorily. Therefore, we have asked whether a humanized AD mouse model can be developed that reflects human AD more faithfully and permit to identify key signals that suffice to induce AD lesions in previously healthy human skin in vivo. Methods: Healthy human skin from non-atopic donors was transplanted onto SCID/ beige mice. After xenotransplant reinnervation by mouse sensory nerve fibers had occurred, mixed autologous human Th2 CD4+ and Tc2 CD8+ T cells that had been pretreated in vitro with IL-2, IL-4, and LPS were injected intradermally into the xenotransplants without skin barrier disruption. Results: Injected non-atopic xenotransplants rapidly developed a morphological, functional, and immunological phenocopy of human AD lesions regarding skin barrier defects, immunopathology including intraepidermal eosinophils, mast cell activation, increase of thymic stromal lymphopoietin, eotaxin-1 and type 2 cytokine circuits, and even showed characteristic neuroimmunological abnormalities such as ß2-adrenergic receptor downregulation. The experimentally induced AD lesions in human skin responded to standard AD therapy (topical dexamethasone or tacrolimus; systemic anti-IL-4Rα antibody [dupilumab]), and relapsed when neurogenic skin inflammation was induced by exposing mice to perceived stress. Conclusions: This new animal model uniquely mimics the complexity of human AD and its clinical response to standard therapy and psychoemotional stressors in vivo, and shows that Th2-polarized lymphocytes associated with excessive IL-4Rα-mediated signaling suffice to induce human AD skin lesions, while atopy and epidermal barrier disruption are dispensable.

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“…Допускается, что расстройства кожного барьера при атопическом дерматите, в том числе повреждения, связанные с зудом, делают кожу атопика более подверженной колонизации золотистым стафилококком, для адгезинов которого открываются дополнительные лиганды: например, фибронектин, лорикрин, цитокератин10 и другие [39]. Кроме того, на фоне повышенной экспрессии цитокинов Th2 профиля, присущей атопическому дерматиту [44], потенцируется действие некоторых факторов вирулентности S. aureus. В частности, активнее идет повреждение и гибель кератиноцитов под влиянием альфатоксина за счет подавления сфингомиелиназы и формирования ламеллярных телец [45].…”

Section: стафилококковая колонизация и вторичная инфекция при атопичеunclassified

Evolving concepts and emerging solutions to the problem of staphylococcal infection in dermatology

Сергеев¹,

Burtseva²,

Сергеева³

2019

Immunopathol Allergol Infectol

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Стафилококки входят в постоянный состав кожной микробиоты и могут вызывать различные инфекции кожи, играя роль и в развитии воспаления при хронических дерматозах. Новые сведения о взаимодействии стафилококков с разными микроорганизмами, кератиноцитами и иммунокомпетентными клетками расширяют наши представления о патогенезе пиодермий, атопического дерматита, акне и другой распространенной патологии кожи. Проблема нарастающей устойчивости стафилококков и, в частности, S. aureus, к наиболее активно используемым антибиотикам вызывает опасения за эффективность химиотерапии инфекций кожи и мягких тканей, в том числе инфекционных осложнений атопического дерматита. Многие ранее использовавшиеся в дерматологии препараты могут выйти из клинического обращения в силу широко распространившейся антибиотикорезистентности к ним в современной популяции. Одними из современных средств, рекомендованных в лечении пиодермии в нашей стране и за рубежом, являются препараты фузидовой кислоты. Проведенное нами в 2009-2019 гг. исследование показало, что в течение 10 лет частота выявления устойчивых к фузидовой кислоте стафилококков у 930 больных хроническими дерматозами выросла не более, чем на 4%, а свыше 90% изученных штаммов оказались чувствительными к препарату. С учетом полученных данных 2% крем и мазь фузидовой кислоты сегодня можно считать средствами первой линии в лечении пиодермии.

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Atopic Dermatitis and Type 2 Immune Deviation

Cited by 6 publications

References 97 publications

Effects of Deacetylasperulosidic Acid on Atopic Dermatitis through Modulating Immune Balance and Skin Barrier Function in HaCaT, HMC-1, and EOL-1 Cells

Effects of Deacetylasperulosidic Acid on Atopic Dermatitis through Modulating Immune Balance and Skin Barrier Function in HaCaT, HMC-1, and EOL-1 Cells

Autologous Th2‐polarized lymphocytes induce atopic dermatitis lesions in non‐atopic human skin xenotransplants

Evolving concepts and emerging solutions to the problem of staphylococcal infection in dermatology

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