The IL-4, IL-13 and IL-31 pathways in atopic dermatitis

Expert Review of Clinical Immunology, Год журнала: 2021, Номер 17(8), С. 835 - 852

Опубликована: Июнь 9, 2021

Introduction: Atopic dermatitis (AD) is the most common inflammatory skin disease. It has a complex pathophysiology, with combination of immune dysregulation and intrinsic barrier defects driving cutaneous inflammation allergic symptomatology. The IL-4, IL-13 IL-31 pathways have been identified as hallmark features in pathogenesis disease, contributing uniquely synergistically to abnormalities well key symptoms, such pruritis. Novel therapeutics that target these under development find treatments for AD.Areas covered: This review discusses AD. We will also detail novel targeted recently or are currently clinical trials A literature search was conducted by querying Scopus, Google Scholar, PubMed, Clinicaltrials.gov up January 2021 using combinations terms 'IL-4' 'IL-13' 'IL-31' 'atopic dermatitis' 'immune pathway' 'biologics' 'novel therapeutics' 'JAK/STAT inhibitors.'Expert opinion: pathophysiology AD advocates innovation. minimally invasive sampling modalities tape stripping allow broader characterization immunomechanisms behind pathophysiology. continued personalized medicine approach treat

Язык: Английский

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From Emollients to Biologicals: Targeting Atopic Dermatitis

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(19), С. 10381 - 10381

Опубликована: Сен. 26, 2021

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease and significantly impacts patients’ lives, particularly in its severe forms. AD clinical presentation varies over course of disease, throughout different age groups, across ethnicities. characterized by a spectrum phenotypes as well endotypes. Starting from current description pathogenesis, this review explores rationale approved therapies emollients to biologicals introduces novel promising drugs.

Язык: Английский

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Atopic dermatitis: pathomechanisms and lessons learned from novel systemic therapeutic options

Journal of the European Academy of Dermatology and Venereology, Год журнала: 2022, Номер 36(9), С. 1432 - 1449

Опубликована: Май 16, 2022

Atopic dermatitis (AD) is a chronic, heterogenous, inflammatory skin disorder associated with high skin-related health burden, typically starting in childhood and often persisting into adulthood. AD characterized by wide range of clinical phenotypes, reflecting multiple underlying pathophysiological mechanisms interactions between genetics, immune system dysregulation environmental factors. In this review, we describe the diverse cellular molecular involved AD, including critical role T-cell-driven inflammation, primarily via T helper (Th) 2- Th17-derived cytokines, many which are mediated Janus kinase (JAK) signaling pathway. These local processes interact sensory neuronal pathways, contributing to manifestations itch, pain sleep disturbance. The recent elucidation pathways has allowed treatment strategies evolve from broad-acting systemic immunosuppressive therapies more targeted agents, JAK inhibitors cytokine-specific biologic agents. Evidence development these reinforced expanded our understanding holds promise for individualized tailored specific subtypes.

Язык: Английский

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Efficacy and safety of baricitinib in combination with topical corticosteroids in patients with moderate-to-severe atopic dermatitis with inadequate response, intolerance or contraindication to ciclosporin: results from a randomized, placebo-controlled, phase III clinical trial (BREEZE-AD4)

British Journal of Dermatology, Год журнала: 2022, Номер 187(3), С. 338 - 352

Опубликована: Апрель 29, 2022

Baricitinib, an oral selective Janus kinase (JAK)1 and JAK 2 inhibitor, was shown to improve the signs symptoms of moderate-to-severe atopic dermatitis (AD).To evaluate efficacy safety baricitinib with background topical corticosteroids (TCS) in patients AD inadequate response, intolerance or contraindication ciclosporin A (CA).In this double-blind, randomized, placebo-controlled, phase III study, were randomized 1: 2: 1 placebo (N = 93), mg 185) 4 92) TCS. The primary endpoint proportion receiving (+ TCS) vs. + TCS who achieved ≥ 75% improvement from baseline Eczema Area Severity Index (EASI 75) at week 16.Baricitinib superior for EASI 75 (4 mg: 32%, placebo: 17%, P 0·031) 16 improvements itch, skin pain number night-time awakenings owing itch. Improvements maintained through 52 weeks treatment. Treatment-emergent adverse events (TEAEs) more common than TCS); most mild moderate. frequent TEAEs nasopharyngitis, herpes simplex, influenza headache. No deaths deep vein thromboses reported.Baricitinib improved treatment CA. profile consistent previous studies AD. What is already known about topic? Ciclosporin indicated that refractory therapies. However, its use limited by concerns it may not provide adequate response some patients. JAK2 has been as a monotherapy combination corticosteroids. does study add? Baricitinib combined low- moderate-potency provided year contraindication, failure respond A. treatment-emergent dermatitis.

Язык: Английский

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Improvement in eosinophilic esophagitis when using dupilumab for other indications or compassionate use

Annals of Allergy Asthma & Immunology, Год журнала: 2022, Номер 128(5), С. 589 - 593

Опубликована: Янв. 25, 2022

Язык: Английский

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Molecular and cellular mechanisms of itch and pain in atopic dermatitis and implications for novel therapeutics

Clinical & Translational Immunology, Год журнала: 2022, Номер 11(5)

Опубликована: Янв. 1, 2022

Atopic dermatitis is a chronic inflammatory skin disease. Patients with atopic experience lesions associated intense itch and pain, which lead to sleep disturbance poor mental health quality of life. We review the molecular mechanisms underlying pain symptoms in discuss current clinical development treatments for moderate-to-severe dermatitis. The pathology includes aberrant immune activation involving significant cross-talk among neuronal cells. Exogenous endogenous triggers modulate stimulation mediators including cytokine/chemokine expression/release by cells, causes inflammation, barrier disruption, growth sensory neurons, pain. These complex interactions cell types are mediated primarily cytokines, but also involve chemokines, neurotransmitters, lipids, proteases, antimicrobial peptides, agonists ion channels or various G protein-coupled receptors. have cytokine profile characterised abnormal levels interleukins 4, 12, 13, 18, 22, 31 33; thymic stromal lymphopoietin; interferon gamma. Cytokine receptors mainly signal through Janus kinase/signal transducer activator transcription pathway. Among emerging novel therapeutics, several kinase inhibitors being developed topical systemic treatment because their potential expression release. changes gene that favourable effects on local release, probably other mediators, thus successfully modulating responsible

Язык: Английский

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Production, Formulation, and Application of Postbiotics in the Treatment of Skin Conditions

Fermentation, Год журнала: 2023, Номер 9(3), С. 264 - 264

Опубликована: Март 7, 2023

The skin microbiome is composed of a complex association bacteria, fungi, and viruses. maintenance commensal microbes essential for preventing the overgrowth pathogenic microorganisms or already present opportunistic pathogens. Thus, development bioactive compounds capable modulating has become an important topic both researchers cosmetic industry. Increasingly, scientific evidence highlights that metabolites derived from probiotics have great potential to prevent diseases affecting skin. These recently been called postbiotics are defined as “preparation inanimate and/or their components confers health benefit on host”. Postbiotics obtained fermentations performed almost exclusively by lactic acid bacteria yeast. Short-chain fatty acids, bacteriocins, organic acids some examples postbiotics. exhibit antimicrobial, immunomodulatory, antioxidant, anti-inflammatory activities. In addition, postbiotic production possesses technological advantages, including high stability increased safety, compared viable probiotics. this article, model large-scale uses in formulations reviewed. results vivo tests treatment alopecia, acne, atopic dermatitis, wound healing discussed. Finally, advances shown based survey main patents filed area

Язык: Английский

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Oral Janus kinase inhibitors for atopic dermatitis

Annals of Allergy Asthma & Immunology, Год журнала: 2023, Номер 130(5), С. 577 - 592

Опубликована: Фев. 1, 2023

Язык: Английский

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Lactobacillus for the treatment and prevention of atopic dermatitis: Clinical and experimental evidence

Frontiers in Cellular and Infection Microbiology, Год журнала: 2023, Номер 13

Опубликована: Фев. 16, 2023

Atopic dermatitis (AD) is a chronic inflammatory skin disease, accompanied by itching and swelling. The main pathological mechanism of AD related to the imbalance between Type 2 helper cells (Th2 cells) 1 (Th1 cells). Currently, no safe effective means treat prevent are available; moreover, some treatments have side effects. Probiotics, such as strains Lactobacillus , can address these concerns via various pathways: i) facilitating high patient compliance; ii) regulating Th1/Th2 balance, increasing IL-10 secretion, reducing cytokines; iii) accelerating maturation immune system, maintaining intestinal homeostasis, improving gut microbiota; iv) symptoms AD. This review describes treatment prevention using 13 species . commonly observed in children. Therefore, includes higher proportion studies on children fewer adolescents adults. However, there also that do not improve even worsen allergies In addition, subset genus relieve has been identified vitro future should include more vivo randomized controlled clinical trials. Given advantages disadvantages mentioned above, further research this area urgently required.

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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