Oral Janus kinase/SYK inhibition (ASN002) suppresses inflammation and improves epidermal barrier markers in patients with atopic dermatitis

Journal of Allergy and Clinical Immunology, Год журнала: 2019, Номер 144(4), С. 1011 - 1024

Опубликована: Июль 26, 2019

Язык: Английский

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Selective JAK1 Inhibitors for the Treatment of Atopic Dermatitis: Focus on Upadacitinib and Abrocitinib

American Journal of Clinical Dermatology, Год журнала: 2020, Номер 21(6), С. 783 - 798

Опубликована: Авг. 10, 2020

Язык: Английский

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A biofabricated vascularized skin model of atopic dermatitis for preclinical studies

Biofabrication, Год журнала: 2020, Номер 12(3), С. 035002 - 035002

Опубликована: Фев. 14, 2020

Three-dimensional (3D) biofabrication techniques enable the production of multicellular tissue models as assay platforms for drug screening. The increased cellular and physiological complexity in these 3D should recapitulate relevant biological environment found body. Here we describe use bioprinting to fabricate skin equivalent tissues varying complexity, including human epidermis, non-vascularized vascularized full-thickness equivalents, a multi-well platform Human keratinocytes, fibroblasts, pericytes, induced pluripotent stem cell-derived endothelial cells were used process produce complexity. equivalents exhibit correct structural markers dermis epidermis stratification, with functions barrier. robustness, versatility reproducibility are further highlighted by generation atopic dermatitis (AD)-disease like tissues. These AD demonstrate several clinical hallmarks disease, including: (i) spongiosis hyperplasia; (ii) early terminal expression differentiation proteins; (iii) increases levels pro-inflammatory cytokines. We show pre-clinical relevance biofabricated disease phenotype testing effects dexamethasone, an anti-inflammatory corticosteroid, three Janus Kinase inhibitors from trials AD. This study demonstrates development versatile reproducible approach create range modeling. In addition, establish readouts that quantifiable, robust, relevant, can be scaled up compound results develops more physiologically model. Thus, this offer vitro rapid understanding pathological mechanisms, efficacy action toxic drugs.

Язык: Английский

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JAK inhibitors for asthma

Journal of Allergy and Clinical Immunology, Год журнала: 2021, Номер 148(4), С. 953 - 963

Опубликована: Окт. 1, 2021

Язык: Английский

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Overview of Atopic Dermatitis in Different Ethnic Groups

Journal of Clinical Medicine, Год журнала: 2023, Номер 12(7), С. 2701 - 2701

Опубликована: Апрель 4, 2023

Atopic dermatitis (AD) is a common chronic inflammatory skin disease with high prevalence worldwide, including countries from Asia, Africa, and Latin America, in different ethnic groups. In recent years, more attention has been placed on the heterogeneity of AD associated multiple factors, patient’s background, resulting an increasing body clinical, genetic, epidemiologic, immune-phenotypic evidence that delineates differences among racial Filaggrin (FLG) mutations, strongest genetic risk factor for development AD, are detected up to 50% European 27% Asian patients, but very rarely Africans. Th2 hyperactivation attribute all groups, though endotype also characterized by increased Th17-mediated signal, whereas African Americans show strong Th2/Th22 signature absence Th1/Th17 skewing. addition, may hold important therapeutic implications as predisposition affect treatment response and, thereby, tailored strategy better targets dominant immunologic pathways each subgroup be envisaged. Nevertheless, white patients represent largest ethnicity enrolled tested clinical trials most treated real-world setting, limiting investigations about safety efficacy across ethnicities. The purpose this review describe pathophysiology ethnicities its potential implications.

Язык: Английский

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Rational design of a JAK1-selective siRNA inhibitor for the modulation of autoimmunity in the skin

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Ноя. 4, 2023

Abstract Inhibition of Janus kinase (JAK) family enzymes is a popular strategy for treating inflammatory and autoimmune skin diseases. In the clinic, small molecule JAK inhibitors show distinct efficacy safety profiles, likely reflecting variable selectivity subtypes. Absolute subtype has not yet been achieved. Here, we rationally design interfering RNAs (siRNAs) that offer sequence-specific gene silencing JAK1, narrowing spectrum action on JAK-dependent cytokine signaling to maintain improve safety. Our fully chemically modified siRNA supports efficient JAK1 expression in human explant modulation JAK1-dependent signaling. A single injection into mouse enables five weeks duration effect. model vitiligo, local administration significantly reduces infiltration autoreactive CD8 + T cells prevents epidermal depigmentation. This work establishes path toward treatments as new class therapeutic modality

Язык: Английский

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Mechanism of action of certain medicinal plants for the treatment of asthma

Journal of Ethnopharmacology, Год журнала: 2023, Номер 317, С. 116828 - 116828

Опубликована: Июнь 25, 2023

Язык: Английский

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Phytochemicals as treatment for allergic asthma: Therapeutic effects and mechanisms of action

Phytomedicine, Год журнала: 2023, Номер 122, С. 155149 - 155149

Опубликована: Окт. 15, 2023

Язык: Английский

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Atopic Dermatitis: Collegium Internationale Allergologicum (CIA) Update 2019

International Archives of Allergy and Immunology, Год журнала: 2019, Номер 178(3), С. 207 - 218

Опубликована: Янв. 1, 2019

Atopic dermatitis (AD) is a chronic inflammatory skin disease presenting with recurrent eczematous lesions and intense pruritus. It common affects both children adults, often beginning in infancy. Due to the unpredictable course, its visible lesions, itching scratching followed by sleeplessness, other associated atopic diseases, behavioral psychiatric disorders, AD an immense burden for patients caregivers. determined genetic predisposition characterized impaired barrier T-helper-2-predominant inflammation. Restoration of main approach treating preventing AD. In order cope acute flares, usually topical corticosteroids (TCS) are applied, while calcineurin inhibitors (TCI) used mainly maintenance therapy. There small group who refractory TCS TCI require systemic immunosuppressive drugs such as ciclosporin. Novel, targeted therapies under clinical investigation, among which anti-IL-4/IL-13 receptor antibody has recently been approved several countries. As we learn understand pathomechanisms AD, characteristics different patient subgroups, effectiveness various therapies, personalized treatment ensuring best efficacy safety and, probably, disease-modifying effect will result.

Язык: Английский

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Selective Janus Kinase 1 Inhibition Is a Promising Therapeutic Approach for Lupus Erythematosus Skin Lesions

Frontiers in Immunology, Год журнала: 2020, Номер 11

Опубликована: Март 3, 2020

Background: Cutaneous lupus erythematosus (CLE) is an interferon (IFN) -driven autoimmune skin disease characterized by extensive cytotoxic lesional inflammation with activation of different innate immune pathways. Aim our study was to investigate the specific role Janus kinase 1 (JAK1) in this and potential benefit selective JAK1 inhibitors as targeted therapy a preclinical CLE model. Methods: Lesional patients subtypes healthy controls (N=31) were investigated on expression IFN-associated mediators via immunohistochemistry gene analyses. The functional efficacy inhibition evaluated vitro using cultured keratinocytes stimulated endogenous nucleic acids. Results confirmed vivo established lupus-prone mouse Results: Proinflammatory pathways, including JAK/STAT signaling, are significantly upregulated within inflamed skin. Here, dermal cells strongly express activated phospho-JAK1. Selective pharmacological reduces typical proinflammatory such CXCL chemokines, BLyS, TRAIL AIM2 models also improves lesions TREX1-/- -mice markedly. Conclusion: plays crucial pathophysiology CLE. leads decrease cytokine expression, reduced decline keratinocyte cell death. Topical treatment JAK1-specific inhibitor CLE-like -mouse model appears be promising therapeutic approach for patients.

Язык: Английский

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