T cell co-stimulatory and co-inhibitory pathways in atopic dermatitis DOI Creative Commons
Chunjiao Zheng, Yuling Shi, Ying Zou

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: March 13, 2023

The use of immune checkpoint inhibitors (ICIs) targeting the T cell inhibitory pathways has revolutionized cancer treatment. However, ICIs might induce progressive atopic dermatitis (AD) by affecting reactivation. critical role cells in AD pathogenesis is widely known. co-signaling regulate activation, where molecules are essential for determining magnitude response to antigens. Given increasing treatment, a timely overview required. In this review, we emphasize importance these involved pathogenesis. We also discuss potential treat and present unresolved issues existing limitations. A better understanding would aid investigation mechanism, prognosis evaluation, treatment AD.

Language: Английский

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

Ana B. Pavel,

Teresa Song, Hyun Je Kim

et al.

Journal of Allergy and Clinical Immunology, Journal Year: 2019, Volume and Issue: 144(4), P. 1011 - 1024

Published: July 26, 2019

Language: Английский

Citations

110
Selective JAK1 Inhibitors for the Treatment of Atopic Dermatitis: Focus on Upadacitinib and Abrocitinib DOI
Sandra Ferreira, Emma Guttman‐Yassky, Tiago Torres

et al.

American Journal of Clinical Dermatology, Journal Year: 2020, Volume and Issue: 21(6), P. 783 - 798

Published: Aug. 10, 2020

Language: Английский

Citations

104
A biofabricated vascularized skin model of atopic dermatitis for preclinical studies DOI
Xue Liu, Sam Michael, Kapil Bharti

et al.

Biofabrication, Journal Year: 2020, Volume and Issue: 12(3), P. 035002 - 035002

Published: Feb. 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.

Language: Английский

Citations

90
JAK inhibitors for asthma DOI
Steve N. Georas,

Patrick Donohue,

Margaret Connolly

et al.

Journal of Allergy and Clinical Immunology, Journal Year: 2021, Volume and Issue: 148(4), P. 953 - 963

Published: Oct. 1, 2021

Language: Английский

Citations

57
Overview of Atopic Dermatitis in Different Ethnic Groups DOI Open Access
Andrea Chiricozzi, Martina Maurelli, Laura Calabrese

et al.

Journal of Clinical Medicine, Journal Year: 2023, Volume and Issue: 12(7), P. 2701 - 2701

Published: April 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.

Language: Английский

Citations

36
Rational design of a JAK1-selective siRNA inhibitor for the modulation of autoimmunity in the skin DOI Creative Commons
Qi Tang, Hassan H. Fakih,

Mohammad Zain UI Abideen

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Nov. 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

Language: Английский

Citations

28
Mechanism of action of certain medicinal plants for the treatment of asthma DOI

Kainat Usmani,

S. K. Jain, Shweta Yadav

et al.

Journal of Ethnopharmacology, Journal Year: 2023, Volume and Issue: 317, P. 116828 - 116828

Published: June 25, 2023

Language: Английский

Citations

19
Phytochemicals as treatment for allergic asthma: Therapeutic effects and mechanisms of action DOI
Seyed Vahid Jasemi, Hosna Khazaei,

Mohammad Reza Morovati

et al.

Phytomedicine, Journal Year: 2023, Volume and Issue: 122, P. 155149 - 155149

Published: Oct. 15, 2023

Language: Английский

Citations

19
Atopic Dermatitis: Collegium Internationale Allergologicum (CIA) Update 2019 DOI Open Access
Dagmar Simon, Andreas Wollenberg, Harald Renz

et al.

International Archives of Allergy and Immunology, Journal Year: 2019, Volume and Issue: 178(3), P. 207 - 218

Published: Jan. 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.

Language: Английский

Citations

53
Selective Janus Kinase 1 Inhibition Is a Promising Therapeutic Approach for Lupus Erythematosus Skin Lesions DOI Creative Commons

Tanja Fetter,

Paul Smith,

Tugce Guel

et al.

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 11

Published: March 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.

Language: Английский

Citations

49