Recent Advancements in the Atopic Dermatitis Mechanism

Frontiers in Bioscience-Landmark, Journal Year: 2024, Volume and Issue: 29(2)

Published: Feb. 22, 2024

Atopic dermatitis (AD) is a recurrent, chronic, inflammatory, itchy skin disorder that affects up to 20% of the pediatric population and 10% adult worldwide. Onset typically occurs early in life, although cardinal disease features are similar across all ages, different age groups ethnicities present distinct clinical characteristics. The imposes significant burden health-related quality life domains, both children adults, substantial economic cost at individual national levels. pathophysiology AD includes complex multifaceted interplay between impaired dysfunctional epidermal barrier, genetic predisposition, environmental contributors, such as chemical and/or biological pollutants allergens, context dysregulated TH2 TH17 skewed immune response. Regarding component, loss function mutations encoding structural proteins filaggrin, fundamental protein, more recently identified variations differentiation well-established determinants resulting an barrier AD. More recently, epigenetic factors have facilitated development, including dysbiotic microbiome effect external exposome, combined with dietary disorders. Notably, interleukin (IL)-31 network, comprising several cell types, macrophages, basophils, generated cytokines involved pathogenesis itch AD, has been explored. Unraveling specific endotypes, highlighting implicated molecular pathogenetic mechanisms clinically relevant phenotypes, emerged crucial step toward targeted therapies for personalized treatment patients. This review aims state-of-the-art knowledge regarding multifactorial interactive pathophysiological

Language: Английский

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Filaggrin and beyond

Annals of Allergy Asthma & Immunology, Journal Year: 2023, Volume and Issue: 132(2), P. 187 - 195

Published: Sept. 25, 2023

Atopic dermatitis (AD) is the most common inflammatory skin disease worldwide, affecting 20% of children and 5% adults. One critical component in pathophysiology AD epidermal barrier, with its outermost layer, stratum corneum (SC), conferring biochemical properties that enable resilience against environmental threats maintain homeostasis. The barrier may be conceptualized as a key facilitator complex interactions between genetics, host immunity, cutaneous microbiome, exposures. genetic risk factor for development persistence loss-of-function mutation FLG, recent advances genomics focusing on rare variant discovery, establishment pathogenic mechanisms, exploration role other differentiation gene variants AD. Aberrant type 2 responses down-regulate transcription genes, alter composition SC lipids, induce further injury through neurocutaneous feedback loop itch-scratch cycle. dysbiotic epidermis exhibits reduced bacterial diversity enhanced colonization Staphylococcus Malassezia species, which contribute to both direct action toxins perpetuation cascades. Enhanced understanding each mechanisms underpinning disruption has led novel topical systemic molecules, including interleukin (IL)-4Ra, IL-13, PDE4, Janus-associated kinase inhibitors, whose clinical effectiveness exceeds conventional treatment modalities. In this narrative review, we aim summarize current above-mentioned pathophysiological therapeutic focus genetic, cellular, molecular development.

Language: Английский

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Epidermal barrier impairment predisposes for excessive growth of the allergy‐associated yeast Malassezia on murine skin

Allergy, Journal Year: 2024, Volume and Issue: 79(6), P. 1531 - 1547

Published: Feb. 22, 2024

Abstract Background The skin barrier is vital for protection against environmental threats including insults caused by skin‐resident microbes. Dysregulation of this a hallmark atopic dermatitis (AD) and ichthyosis, with variable consequences host immune control colonizing commensals opportunistic pathogens. While Malassezia the most abundant commensal fungus skin, little known about in inflammatory diseases. Methods In experimental study, MC903‐treated mice were colonized spp. to assess host–fungal interactions dermatitis. Additional murine models AD tape stripping, K5‐Nrf2 overexpression flaky tail mice, employed confirm expand findings. Skin fungal counts enumerated. High parameter flow cytometry was used characterize antifungal response AD‐like skin. Structural functional alterations determined histology transcriptomics bulk Finally, differential expression metabolic genes quantified. Results grows excessively Fungal overgrowth could, however, not be explained altered status Instead, we found that upregulating key cutaneous niche, acquired enhanced fitness efficiently colonise impaired barrier. Conclusions This study provides evidence structural changes dysfunctional epidermal environment provide increased accessibility an lipid profile, which lipid‐dependent yeast adapts nutrient assimilation. Our findings reveal fundamental insights into implication mycobiota pathogenesis common disorders.

Language: Английский

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From Skin and Gut to the Brain: The Infectious Journey of the Human Commensal Fungus Malassezia and Its Neurological Consequences

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: unknown

Published: June 14, 2024

Language: Английский

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Recognizing secondary infection in patients with atopic dermatitis: Head & neck atopic dermatitis

Meditsinskiy sovet = Medical Council, Journal Year: 2025, Volume and Issue: 2, P. 42 - 48

Published: March 30, 2025

Atopic dermatitis is a hereditary chronic skin disease characterized by severe itching, recurrent course and association with other diseases of atopic nature, as well numerous complications, which include the addition secondary infection. Head neck (HNAD) special phenotype that occurs in adolescents adults. A characteristic feature HNAD lesion areas rich sebaceous glands (face, neck, upper third chest back), associated active participation Malassezia fungi pathogenesis dermatosis. The multifactorial HNAD, often persistent course, impossibility complete elimination provoking factor, bacterial infection against background necessitate comprehensive approach to treatment this condition use combination drugs containing glucocorticosteroid, an antimycotic antibiotic relieve exacerbations. article examines etiology, mechanisms development clinical features, modern methods therapy, practical application demonstrated example: patient, 19 years old, complaining itchy, flaky rashes face area, existing for 3 weeks. Based on picture, diagnosis was made: neck. Given multifaceted cause condition, namely both pronounced immune response AD, colonization fungi, open “gates” form erosions, prescription topical glucocorticosteroid pathogenetically justified.

Language: Английский

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A multidimensional analysis of prognostic factors in atopic dermatitis

Frontiers in Medicine, Journal Year: 2025, Volume and Issue: 12

Published: April 17, 2025

Atopic dermatitis (AD) is a chronic inflammatory skin condition with high prevalence worldwide and multifaceted pathogenesis. In general, patients moderate to severe AD often experience relapse after discontinuing treatment. Therefore, understand the possible factors of look for biological markers that predict or poor prognosis will be helpful clinical Mutations in genes such as FLG, SPINK5, STAT, KIF3A, claudin-1, Ovol1, HLA-DRB1 offer new insights into genetic basis AD. Routine may help improve patient lifestyle, highlight importance environmental influences (including psychological stress), support clinicians optimizing anti-infective treatment strategies. The axis (CD30–CD30L axis, IL-9-IL-18 axis) provides pathways target future therapies. Low NKG2D expression have adverse effects on prognosis. Prognostic biomarkers can play an important role monitoring, disease progression recurrence, provide possibility more personalized

Language: Английский

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New insights into allergic rhinitis treatment: MSC nanovesicles targeting dendritic cells

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Sept. 19, 2024

Allergic rhinitis (AR) is a condition with limited treatment options. This study investigates the potential use of mesenchymal stem cell (MSC) nanovesicles as novel therapy for AR. Specifically, explores underlying mechanisms MSC nanovesicle by targeting dendritic cells (DCs). The researchers fabricated DC-targeted P-D2-EVs and characterized their properties. Transcriptomic sequencing single-cell analyses were performed to impact on AR mice, identifying core genes involved in treatment. In vitro experiments conducted validate effects DC metabolism, Th2 differentiation, ILC2 activation. results showed that efficiently targeted DCs. analysis revealed differential expression 948 nasal tissue DCs mice treated P-D2-EVs. Single-cell further had inhibitory activation, Fut1 identified gene. Validation demonstrated improved IL10 metabolism downregulating expression, thereby suppressing differentiation Animal confirmed ability ameliorate symptoms mice. suggests reshape suppress activation through inhibition Fut1/ICAM1/P38 MAPK signaling pathway, providing therapeutic approach

Language: Английский

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Atopic Dermatitis and Psoriasis: Similarities and Differences in Metabolism and Microbiome

Clinical Reviews in Allergy & Immunology, Journal Year: 2024, Volume and Issue: 66(3), P. 294 - 315

Published: July 2, 2024

Language: Английский

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The frontline of alternatives to animal testing: novel in vitro skin model application in drug development and evaluation

Toxicological Sciences, Journal Year: 2023, Volume and Issue: 196(2), P. 152 - 169

Published: Sept. 12, 2023

Abstract The FDA Modernization Act 2.0 has brought nonclinical drug evaluation into a new era. In vitro models are widely used and play an important role in modern development evaluation, including early candidate screening preclinical efficacy toxicity assessment. Driven by regulatory steering facilitated well-defined physiology, novel skin emerging rapidly, becoming the most advanced area alternative testing research. revolutionary technologies bring us many models, either laboratory-developed or commercially available, which were all built to emulate structure of natural recapitulate skin’s physiological function particular pathology. During model development, how achieve balance among complexity, accessibility, capability, cost-effectiveness remains core challenge for researchers. This review attempts introduce existing align them on different dimensions, such as structural functional maturity, throughput, provide update their current application various scenarios within scope chemical genotoxicity, phototoxicity, sensitization, corrosion/irritation. Overall, will summarize general strategy enhance future invention, application, translation evaluation.

Language: Английский

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The mycobiome in atopic diseases: Inducers and triggers

Journal of Allergy and Clinical Immunology, Journal Year: 2023, Volume and Issue: 152(6), P. 1368 - 1375

Published: Oct. 19, 2023

Atopic diseases are characterized by type 2 inflammation, with high levels of allergen-specific T

Language: Английский

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