Mechanisms of melanocyte death in vitiligo

Medicinal Research Reviews, Год журнала: 2020, Номер 41(2), С. 1138 - 1166

Опубликована: Ноя. 17, 2020

Abstract Vitiligo is an autoimmune depigment disease results from extensive melanocytes destruction. The destruction of melanocyte thought to be multifactorial causation. Genome‐wide associated studies have identified single‐nucleotide polymorphisms in a panel susceptible loci as risk factors death. But vitiligo onset can't solely attributed susceptive genetic background. Oxidative stress triggered by elevated levels reactive oxygen species accounts for melanocytic molecular and organelle dysfunction, minority demise, melanocyte‐specific antigens exposure. Of note, the self‐responsive immune function directly contributes bulk deaths vitiligo. aberrantly heightened innate immunity, type‐1‐skewed T helper, incompetent regulatory cells tip balance toward autoreaction CD8 + cytotoxic lymphocytes finally execute killing melanocytes, possibly alarmed resident memory cells. In addition well‐established apoptosis necrosis, we discuss several death modalities like oxeiptosis, ferroptosis, necroptosis that are probably employed This review focuses on various mechanisms pathogenesis demonstrate panorama that. We hope provide new insights into treatment strategies review.

Язык: Английский

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Two Phase 3, Randomized, Controlled Trials of Ruxolitinib Cream for Vitiligo

New England Journal of Medicine, Год журнала: 2022, Номер 387(16), С. 1445 - 1455

Опубликована: Окт. 19, 2022

Vitiligo is a chronic autoimmune disease that causes skin depigmentation. A cream formulation of ruxolitinib (an inhibitor Janus kinase 1 and 2) resulted in repigmentation phase 2 trial involving adults with vitiligo.We conducted two 3, double-blind, vehicle-controlled trials (Topical Ruxolitinib Evaluation Study [TRuE-V1] [TRuE-V2]) North America Europe involved patients 12 years age or older who had nonsegmental vitiligo depigmentation covering 10% less total body-surface area. Patients were randomly assigned 2:1 ratio to apply 1.5% vehicle control twice daily for 24 weeks all areas on the face body, after which could through week 52. The primary end point was decrease (improvement) at least 75% from baseline facial Area Scoring Index (F-VASI; range, 0 higher scores indicating greater area depigmentation), F-VASI75 response, 24. There five key secondary points, including improved responses Noticeability Scale.A 674 enrolled, 330 TRuE-V1 344 TRuE-V2. In TRuE-V1, percentage an response 29.8% ruxolitinib-cream group 7.4% (relative risk, 4.0; 95% confidence interval [CI], 1.9 8.4; P<0.001). TRuE-V2, percentages 30.9% 11.4%, respectively 2.7; CI, 1.5 4.9; results points showed superiority over control. Among applied throughout 52 weeks, adverse events occurred 54.8% 62.3% TRuE-V2; most common application-site acne (6.3% 6.6%, respectively), nasopharyngitis (5.4% 6.1%), pruritus 5.3%).In 3 trials, application lesions than but it associated site. Larger longer are required determine effect safety vitiligo. (Funded by Incyte; TRuE-V2 ClinicalTrials.gov numbers, NCT04052425 NCT04057573.).

Язык: Английский

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Evidence of pyroptosis and ferroptosis extensively involved in autoimmune diseases at the single-cell transcriptome level

Journal of Translational Medicine, Год журнала: 2022, Номер 20(1)

Опубликована: Авг. 12, 2022

Approximately 8-9% of the world's population is affected by autoimmune diseases, and yet mechanism autoimmunity trigger largely understudied. Two unique cell death modalities, ferroptosis pyroptosis, provide a new perspective on mechanisms leading to development treatment strategies.Using scRNA-seq datasets, aberrant trend pyroptosis-related genes were analyzed in several representative diseases (psoriasis, atopic dermatitis, vitiligo, multiple sclerosis, systemic sclerosis-associated interstitial lung disease, Crohn's experimental orchitis). Cell line models also assessed using bulk RNA-seq qPCR.A substantial difference was observed between normal disease samples involving pyroptosis. In present study, pyroptosis showed an imbalance different keratinocyte lineages psoriatic skinin addition pyroptosis-sensitive subset dermatitis (AD) skin. The results revealed that are involved epidermal melanocyte destruction vitiligo. Aberrant has been detected orchitis. adopted study identified pro-inflammatory factors can drive changes pyroptosis.These involvement pathological process at level. IFN-γ critical inducer sensitivity, two models.

Язык: Английский

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The Role of Oxidative Stress in Vitiligo: An Update on Its Pathogenesis and Therapeutic Implications

Cells, Год журнала: 2023, Номер 12(6), С. 936 - 936

Опубликована: Март 19, 2023

Vitiligo is an autoimmune skin disorder caused by dysfunctional pigment-producing melanocytes which are attacked immune cells. Oxidative stress considered to play a crucial role in activating consequent responses related vitiligo. Melanin synthesis the main intracellular stressor, producing reactive oxygen species (ROS). Under normal physiological conditions, antioxidative nuclear factor erythroid 2-related 2 (Nrf2) pathway functions as mediator for cells resist oxidative stress. In pathological situations, such with antioxidant defects or under inflammation, ROS accumulate and cause cell damage. Herein, we summarize events at cellular level excessive vitiligo highlight exposure melanocyte-specific antigens that trigger responses. Such lead functional impairment death of melanocytes, sequentially increase melanocyte cytotoxicity through both innate adaptive immunity. This report provides new perspectives advances our understanding interrelationships between autoimmunity pathogenesis We describe progress targeted therapy, aim providing potential therapeutic approaches.

Язык: Английский

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Preparation of Ethosome Gel with Total Flavonoids from Vernonia anthelmintica (L.) Willd. for the Treatment of Vitiligo

Gels, Год журнала: 2025, Номер 11(1), С. 73 - 73

Опубликована: Янв. 17, 2025

Vernonia anthelmintica (L.) Willd. is a traditional medicinal herb in Chinese medicine, extensively used by various ethnic groups due to the numerous advantages derived from its total flavonoids. These benefits encompass anti-inflammatory and antioxidant effects, promotion of melanin production, showcasing significant efficacy addressing vitiligo. To improve transdermal absorption enhance effectiveness treatment, ethosome containing flavonoids were prepared utilizing ultrasound injection technique. The resulting was then carefully mixed with 0.7% Carbomer 934 gel equal parts, yielding concentration 0.302 mg/g. This formulation produced small, consistent that exhibited high encapsulation efficiency notable stability. In vitro analyses demonstrated sustained release characteristics considerable therapeutic against vitiligo hydroquinone exposure. Histological examinations performed through hematoxylin eosin (H&E) staining mouse skin revealed increased production activities tyrosinase (TYR), cholinesterase (CHE), monoamine oxidase (MAO), while levels superoxide dismutase (SOD) malondialdehyde (MDA) reduced. findings underscore promising this treatment strategy validate dosage form.

Язык: Английский

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Clinical Features, Immunopathogenesis, and Therapeutic Strategies in Vitiligo

Clinical Reviews in Allergy & Immunology, Год журнала: 2021, Номер 61(3), С. 299 - 323

Опубликована: Июль 20, 2021

Язык: Английский

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Characteristics and pathogenesis of Koebner phenomenon

Experimental Dermatology, Год журнала: 2022, Номер 32(4), С. 310 - 323

Опубликована: Ноя. 17, 2022

The Koebner phenomenon, also known as isomorphic reaction, refers to the development of secondary lesions with same clinical manifestations and histopathological characteristics primary in normal skin after trauma or other stimuli. triggering factors phenomenon include physical trauma, chemical stimulation, mechanical stress, iatrogenic stimulation pathogenic infection. Vitiligo, psoriasis lichen planus are considered true phenomenon. Recent studies have shown that immunological disorders, oxidative defective melanocyte adhesion growth factor deficiency main pathological mechanisms vitiligo In psoriasis, triggers may drive inflammation induce a psoriatic phenotype through multiple signalling pathways thereby cause susceptible individuals. Significantly, keratinocytes mediate occurrence mechano-induced sensing signals explains high frequency on extensor side elbow knee joints. On contrary, TRPA1-driven mechano-transduction, autoimmunity actinic damage underlying planus. this review, we summarized current understanding pathogenesis

Язык: Английский

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Oxeiptosis: a novel pathway of melanocytes death in response to oxidative stress in vitiligo

Cell Death Discovery, Год журнала: 2022, Номер 8(1)

Опубликована: Фев. 17, 2022

Vitiligo is a cutaneous depigmenting autoimmune disease caused by the extensive destruction of epidermal melanocytes. Convincing data has defined critical role for oxidative stress in pathogenesis vitiligo. Oxeiptosis caspase-independent cell death modality that was reportedly triggered and operative pathogen clearance. However, whether oxeiptosis exists stress-induced melanocytes demise vitiligo remains undetermined. In present study, we initially found other modalities might exist addition to well-recognized apoptosis necroptosis H2O2-treated Furthermore, AIFM1 be dephosphorylated at Ser116 death, which specific oxeiptosis. Moreover, KEAP1 PGAM5, upstream oxeiptosis, were operate melanocytic death. Subsequently, KEAP1-PGAM5-AIFM1 signaling pathway proved involved stress-triggered through depletion PGAM5. Altogether, our study indicated occur under contribute

Язык: Английский

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How Does Vitamin D Affect Immune Cells Crosstalk in Autoimmune Diseases?

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(5), С. 4689 - 4689

Опубликована: Фев. 28, 2023

Vitamin D is a secosteroid hormone that highly involved in bone health. Mounting evidence revealed that, addition to the regulation of mineral metabolism, vitamin implicated cell proliferation and differentiation, vascular muscular functions, metabolic Since discovery receptors T cells, local production active was demonstrated most immune addressing interest clinical implications status surveillance against infections autoimmune/inflammatory diseases. together with B are seen as main cells autoimmune diseases; however, growing currently focused on innate compartment, such monocytes, macrophages, dendritic natural killer initiation phases autoimmunity. Here we reviewed recent advances onset Graves’ Hashimoto’s thyroiditis, vitiligo, multiple sclerosis relation role their crosstalk acquired cells.

Язык: Английский

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Different types of cell death in diabetic endothelial dysfunction

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 168, С. 115802 - 115802

Опубликована: Окт. 31, 2023

Diabetes mellitus is a metabolic disease caused by disorders of insulin secretion and utilization. Long-term hyperglycemia, resistance, glucose lipid metabolism cause vascular endothelial cell damage. Endothelial dysfunction key feature diabetic complications such as nephropathy, retinopathy, neuropathy, atherosclerosis. Importantly, death thought to be factor contributing injury. Morphologically, can divided into three forms: type I apoptosis, II autophagy, III necrosis. According the difference in function, accidental (ACD) regulated (RCD). RCD controlled process involving numerous proteins precise signaling cascades. Multiple subroutines covered may involved dysfunction, including necroptosis, pyroptosis, entosis, ferroptosis, ferroautophagy, parthanatos, netotic death, lysosome-dependent alkaliptosis, oxeiptosis, cuproptosis, PANoptosis. This article briefly reviews mechanism significance associated with which will help deepen understanding provide new therapeutic ideas.

Язык: Английский

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