Skin, gut, and lung barrier: Physiological interface and target of intervention for preventing and treating allergic diseases

Allergy, Год журнала: 2024, Номер 79(6), С. 1485 - 1500

Опубликована: Март 4, 2024

The epithelial barriers of the skin, gut, and respiratory tract are critical interfaces between environment host, they orchestrate both homeostatic pathogenic immune responses. mechanisms underlying barrier dysfunction in allergic inflammatory conditions, such as atopic dermatitis, food allergy, eosinophilic oesophagitis, rhinitis, chronic rhinosinusitis, asthma, complex influenced by exposome, microbiome, individual genetics, epigenetics. Here, we review role digestive tract, airways maintaining homeostasis, how influence occurrence progression current treatments target epithelium to improve symptoms these disorders, what unmet needs identification treatment disorders.

Язык: Английский

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Atopic dermatitis

The Lancet, Год журнала: 2025, Номер 405(10478), С. 583 - 596

Опубликована: Фев. 1, 2025

Язык: Английский

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Filaggrin and beyond

Annals of Allergy Asthma & Immunology, Год журнала: 2023, Номер 132(2), С. 187 - 195

Опубликована: Сен. 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.

Язык: Английский

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Challenges and Future Trends in Atopic Dermatitis

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(14), С. 11380 - 11380

Опубликована: Июль 12, 2023

Atopic dermatitis represents a complex and multidimensional interaction that potential fields of preventive therapeutic management. In addition to the treatment armamentarium available for atopic dermatitis, novel drugs targeting significant molecular pathways in biologics small molecules are also being developed given condition’s pathophysiology. While most patients expecting better efficacy long-term control, response these would still depend on numerous factors such as genotype, diverse environmental triggers microbiome-derived signals, and, importantly, dynamic immune responses. This review article highlights challenges recently pharmacological agents based pathogenesis this condition, creating specific approach toward more personalized medicine.

Язык: Английский

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Dupilumab-associated head and neck dermatitis shows a pronounced type 22 immune signature mediated by oligoclonally expanded T cells

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Апрель 2, 2024

Abstract Dupilumab, an IL4R-blocking antibody, has shown clinical efficacy for atopic dermatitis (AD) treatment. In addition to conjunctivitis/blepharitis, the de novo appearance of head/neck is now recognized as a distinct side effect, occurring in up 10% patients. Histopathological features from AD suggest drug but exact underlying mechanisms remain unknown. We profiled punch biopsies dupilumab-associated head and neck (DAHND) by using single-cell RNA sequencing compared data with untreated healthy control skin. show that dupilumab treatment was accompanied normalization IL-4/IL-13 downstream activity markers such CCL13, CCL17 , CCL18 CCL26 . By contrast, we found strong increases type 22-associated ( IL22, AHR ) especially oligoclonally expanded T cells, enhanced keratinocyte activation IL-22 receptor upregulation. Taken together, demonstrate effectively dampens conventional 2 inflammation DAHND lesions, concomitant hyperactivation IL22 -associated responses.

Язык: Английский

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Nanotechnology strategies to address challenges in topical and cellular delivery of siRNAs in skin disease therapy

Advanced Drug Delivery Reviews, Год журнала: 2024, Номер 207, С. 115198 - 115198

Опубликована: Фев. 9, 2024

Язык: Английский

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Unraveling Atopic Dermatitis: Insights into Pathophysiology, Therapeutic Advances, and Future Perspectives

Cells, Год журнала: 2024, Номер 13(5), С. 425 - 425

Опубликована: Фев. 28, 2024

Atopic dermatitis (AD) is an inflammatory skin condition that frequently develops before the onset of allergic rhinitis or asthma. More than 10% children are affected by this serious condition, which painful for sufferers. Recent research has connected environment, genetics, barrier, drugs, psychological factors, and immune system to severity AD. The causes consequences AD its cellular molecular origins reviewed in paper. exploration interleukins their influence on immunological pathway been facilitated using relevant biomarkers clinical trials. This approach enables identification novel therapeutic modalities, fostering potential targeted translational within realm personalized medicine. review focuses AD’s pathophysiology ever-changing landscape. Beyond plethora biologic medications various stages approval development, a range non-biologic therapies, specifically small molecules, have emerged. These include Janus kinase (JAK) inhibitors like Baricitinib, Upadacitinib, Abrocitinib, thus expanding spectrum options. also addresses latest efficacy data elucidates scientific rationale behind each treatment atopic dermatitis.

Язык: Английский

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Atopic Dermatitis Itch: Scratching for an Explanation

Journal of Investigative Dermatology, Год журнала: 2024, Номер 144(5), С. 978 - 988

Опубликована: Фев. 16, 2024

Язык: Английский

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An OX-Tra’Ordinary Tale: The Role of OX40 and OX40L in Atopic Dermatitis

Cells, Год журнала: 2024, Номер 13(7), С. 587 - 587

Опубликована: Март 28, 2024

The transmembrane glycoprotein OX40 receptor (OX40) and its ligand, OX40L, are instrumental modulators of the adaptive immune response in humans. functions as a costimulatory molecule that promotes T cell activation, differentiation, survival through ligation with OX40L. cells play an integral role pathogenesis several inflammatory skin conditions, including atopic dermatitis (AD). In particular, helper 2 (TH2) strongly contribute to AD via production cytokines associated type inflammation (e.g., IL-4, IL-5, IL-13, IL-31) lead barrier dysfunction pruritus. OX40-OX40L interaction also activation proliferation other populations TH1, TH22, TH17), patients have demonstrated higher levels expression on peripheral blood mononuclear than healthy controls. As such, pathway is potential target for treatment. Novel therapies targeting currently development, which promising safety efficacy results moderate-to-severe AD. Herein, we review function signaling pathway, their pathogenesis, emerging may offer insights into future management.

Язык: Английский

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Anti-Inflammatory Effects of Cannabigerol In Vitro and In Vivo Are Mediated Through the JAK/STAT/NFκB Signaling Pathway

Cells, Год журнала: 2025, Номер 14(2), С. 83 - 83

Опубликована: Янв. 9, 2025

Cannabinoid compounds have potential as treatments for a variety of conditions, with cannabigerol (CBG) being known its anti-inflammatory properties. In this study, we investigated the effects CBG in cellular model 1-chloro-2,4-dinitrobenzene (DNCB)-induced atopic dermatitis (AD). model, confirmed cytotoxicity and downregulated expression inflammatory markers CCL26, IL1B, IL6, TNF (p < 0.001). mouse clinical, histological, immunological changes were analyzed. The results showed that improved severity score, epidermal thickness, mast cell count reduced cytokines (Tslp, Il1b, Il4, Il6, Il13, Il17, Il18, Il22, Il33) by qRT-PCR Western blot modulated JAK1, JAK2, TYK2, STAT1, STAT2, STAT3, p-STAT3, STAT6, p-STAT6 0.05). Subsequently, p-IκBα, NF-κB, p-NF-κB signaling factors also 0.05), corresponding skin barrier factors. study indicate effectively alleviates AD-like symptoms suggest therapeutic agent.

Язык: Английский

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