Type 2 chronic inflammatory diseases: targets, therapies and unmet needs

Nature Reviews Drug Discovery, Journal Year: 2023, Volume and Issue: 22(9), P. 743 - 767

Published: Aug. 1, 2023

Language: Английский

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The skin barrier: An extraordinary interface with an exceptional lipid organization

Progress in Lipid Research, Journal Year: 2023, Volume and Issue: 92, P. 101252 - 101252

Published: Sept. 4, 2023

The barrier function of the skin is primarily located in stratum corneum (SC), outermost layer skin. SC composed dead cells with highly organized lipid lamellae intercellular space. As matrix forms only continuous pathway, lipids play an important role permeation compounds through SC. main classes are ceramides (CERs), cholesterol (CHOL) and free fatty acids (FFAs). Analysis crucial importance understanding function, not healthy skin, but also inflammatory diseases impaired barrier. In this review we provide (i) a historical overview steps undertaken to obtain information on composition organization diseases, ii) CERs, CHOL FFAs phase behavior very complex model systems how knowledge can be used understand deviation iii) both, CER subclasses chain length distribution, membrane permeability simple synthetic FFAs, iv) similarity different species systems, vi) future directions modulating that expected improve diseases.

Language: Английский

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Dupilumab in Inflammatory Skin Diseases: A Systematic Review

Biomolecules, Journal Year: 2023, Volume and Issue: 13(4), P. 634 - 634

Published: March 31, 2023

Dupilumab was first approved for the treatment of atopic dermatitis (AD) and blocks signaling interleukin (IL)-4 -13. Several other chronic skin conditions share mechanistic overlaps with AD in their pathophysiology, i.e., are linked to type 2 inflammation. Most recently, dupilumab by U.S. Food Drug Administration prurigo nodularis (PN). Given its relatively good safety profile, effective off-label use has been reported a multitude dermatologic diseases several clinical trials currently ongoing. We conducted systematic review applications dermatology than PN searching databases PubMed/Medline, Scopus, Web Science Cochrane Library as well trial registry ClinicalTrials.gov. found reports bullous autoimmune diseases, eczema, prurigo, alopecia areata, spontaneous urticaria, Netherton syndrome variety inflammatory diseases.

Language: Английский

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Recent advances in the epithelial barrier theory

International Immunology, Journal Year: 2024, Volume and Issue: 36(5), P. 211 - 222

Published: Jan. 16, 2024

Abstract The epithelial barrier theory links the recent rise in chronic non-communicable diseases, notably autoimmune and allergic disorders, to environmental agents disrupting barrier. Global pollution toxic agent exposure have worsened over six decades because of uncontrolled growth, modernization, industrialization, affecting human health. Introducing new chemicals without any reasonable control their health effects through these years has led documented adverse effects, especially on skin mucosal barriers. These substances, such as particulate matter, detergents, surfactants, food emulsifiers, micro- nano-plastics, diesel exhaust, cigarette smoke, ozone, been shown compromise integrity. This disruption is linked opening tight-junction barriers, inflammation, cell death, oxidative stress, metabolic regulation. Consideration must be given interplay underlying inflammatory medications, affected tissues. review article discusses detrimental effect barrier-damaging compounds involves cellular molecular mechanisms.

Language: Английский

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Rapid reduction in Staphylococcus aureus in atopic dermatitis subjects following dupilumab treatment

Journal of Allergy and Clinical Immunology, Journal Year: 2023, Volume and Issue: 152(5), P. 1179 - 1195

Published: June 13, 2023

Atopic dermatitis (AD) is an inflammatory disorder characterized by dominant type 2 inflammation leading to chronic pruritic skin lesions, allergic comorbidities, and Staphylococcus aureus colonization infections. S thought play a role in AD severity.

Language: Английский

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Targeting Skin Barrier Function in Atopic Dermatitis

The Journal of Allergy and Clinical Immunology In Practice, Journal Year: 2023, Volume and Issue: 11(5), P. 1335 - 1346

Published: Feb. 20, 2023

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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The immunological and structural epidermal barrier dysfunction and skin microbiome in atopic dermatitis-an update

Frontiers in Molecular Biosciences, Journal Year: 2023, Volume and Issue: 10

Published: Aug. 16, 2023

Atopic dermatitis (AD) is a common, chronic and relapsing inflammatory skin disease with various clinical presentations combinations of symptoms. The pathophysiology AD complex multifactorial. There are several factors involved in the etiopathogenesis including structural immunological epidermal barrier defect, imbalance microbiome, genetic background environmental factors. Alterations proteins, lipids, proteases, their inhibitors, lead to impairment stratum corneum which associated increased penetration transepidermal water loss. elevated serum immunoglobulin E levels blood eosinophilia have been shown majority patients. Type 2 T-helper cell immune pathway expression interleukin (IL)-4, IL-5, IL-13, has an important role AD. Both T cells keratinocytes contribute via dynamic interaction cytokines chemokines. microbiome another factor relevance It that during flares, Staphylococcus aureus (S. aureus) colonization increased, while epidermidis epidermidis) decreased. On contrary, S. species Streptococcus, Corynebacterium Propionibacterium remision phases. However, it not clear whether dysbiosis one symptoms or causes therapeutic options, targeting these pathways play critical Although topical steroids mainstay treatment AD, new biological therapies IL-4, IL-31 as well Janus kinase inhibitors (JAKi), increasingly gain more importance advances therapy In this review, we summarize dysfunction, abnormalities, filaggrin mutation options for effects on abnormalities skin.

Language: Английский

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Skin Barrier in Atopic Dermatitis

Journal of Investigative Dermatology, Journal Year: 2024, Volume and Issue: 144(5), P. 989 - 1000.e1

Published: April 19, 2024

Language: Английский

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Blockade of IL-13 signaling improves skin barrier function and biology in patients with moderate to severe atopic dermatitis

British Journal of Dermatology, Journal Year: 2024, Volume and Issue: 191(3), P. 344 - 350

Published: March 26, 2024

Abstract Background Interleukin (IL)-13 is a key driver of inflammation and barrier dysfunction in atopic dermatitis (AD). While there robust evidence that tralokinumab – monoclonal antibody neutralizes IL-13 reduces clinical disease activity, less known about its effects on function. Objectives To characterize the treatment skin Methods Transepidermal water loss (TEWL), stratum corneum hydration (SCH), natural moisturizing factor content, histopathological characteristics, biomarker expression microbiome composition were evaluated lesional, nonlesional sodium lauryl sulfate-irritated 16 patients with AD over course weeks treatment. Results All severity scores decreased significantly time. At week 16, mean TEWL target lesions by 33% (P = 0.01) SCH increased 58% 0.004), along histological reduction spongiosis 0.003), keratin epidermal thickness 0.001). In parallel, was significant decrease several dysfunction-associated proinflammatory proteins such as fibronectin 0.006), CCL17/TARC 0.03) IL-8 0.01), changes seen early 8. Total bacterial load Staphylococcus aureus abundance reduced from 2. Conclusions Tralokinumab improved physiology, pathology dysbiosis, further highlighting pleiotropic role pathogenesis.

Language: Английский

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