ArticleThe Journal of investigative dermatology2016
AP1S3 Mutations Cause Skin Autoinflammation by Disrupting Keratinocyte Autophagy and Up-Regulating IL-36 Production.
Article in The Journal of investigative dermatology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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Who cites it
85 citing papers in PubMed, 152 citations in OpenAlex.
- IL-36-Driven Inflammation in Generalized Pustular Psoriasis: Immunological Insights from Plaque Psoriasis and Implications for Targeted Therapy.International journal of molecular sciences · 2026Review
- Repeated Episodes of GPP Induced by Respiratory Infections Are Mediated by Loss-of-Function IFIH1.Immunity, inflammation and disease · 2026Article
- Autophagy and mitophagy in dermatological disease: a comprehensive review from molecular pathways to therapeutic frontiers.Biology direct · 2025Review
- Considerations for Treating Generalized Pustular Psoriasis (GPP): A Narrative Review.Dermatology and therapy · 2025Review
- Targeting the IL-36 receptor with spesolimab mitigates residual inflammation and prevents generalized pustular psoriasis flares.The Journal of clinical investigation · 2025Article
- Considerations for defining and diagnosing generalized pustular psoriasis.Journal of the European Academy of Dermatology and Venereology : JEADV · 2025Review
- Updated genetic background of generalized pustular psoriasis as an autoinflammatory keratinization disease.The Journal of dermatology · 2025Review
- Dialogue between programmed cell death and psoriasis.Postepy dermatologii i alergologii · 2025Review
- Chaperone-mediated autophagy dysfunction in imiquimod-induced psoriasiform dermatitis.Autophagy reports · 2025Article
- An AAGAB-to-CCDC32 handover mechanism controls the assembly of the AP2 adaptor complex.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Functional Genomics and Insights into the Pathogenesis and Treatment of Psoriasis.Biomolecules · 2024Review
- Pediatric psoriasis: Understanding pathological conditions and advances in treatment.The Journal of dermatology · 2024Review
- Diseases categorized as autoinflammatory keratinization diseases (AiKDs), and their pathologies and treatments.Nagoya journal of medical science · 2024Review
- Multi-Omics Approach to Improved Diagnosis and Treatment of Atopic Dermatitis and Psoriasis.International journal of molecular sciences · 2024Review
- The multifaceted role of autophagy in skin autoimmune disorders: a guardian or culprit?Frontiers in immunology · 2024Review
- Skin barrier-inflammatory pathway is a driver of the psoriasis-atopic dermatitis transition.Frontiers in medicine · 2024Review
- Mechanisms of autophagy and their implications in dermatological disorders.Frontiers in immunology · 2024Review
- Successful treatment of acrodermatitis continua of Hallopeau coexisting with generalized pustular psoriasis with spesolimab: a case report.Frontiers in immunology · 2024Article
- Autoinflammatory Keratinization Diseases-The Concept, Pathophysiology, and Clinical Implications.Clinical reviews in allergy & immunology · 2023Review
- Phytocannabinoids Reduce Inflammation of Primed Macrophages and Enteric Glial Cells: An In Vitro Study.International journal of molecular sciences · 2023Article
25 more citing papers are in PubMed but not listed here.
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Authors and funding
26 authors at 17 institutions in 11 countries.
Funding
Abstract
Prominent skin involvement is a defining characteristic of autoinflammatory disorders caused by abnormal IL-1 signaling. However, the pathways and cell types that drive cutaneous autoinflammatory features remain poorly understood. We sought to address this issue by investigating the pathogenesis of pustular psoriasis, a model of autoinflammatory disorders with predominant cutaneous manifestations. We specifically characterized the impact of mutations affecting AP1S3, a disease gene previously identified by our group and validated here in a newly ascertained patient resource. We first showed that AP1S3 expression is distinctively elevated in keratinocytes. Because AP1S3 encodes a protein implicated in autophagosome formation, we next investigated the effects of gene silencing on this pathway. We found that AP1S3 knockout disrupts keratinocyte autophagy, causing abnormal accumulation of p62, an adaptor protein mediating NF-κB activation. We showed that as a consequence, AP1S3-deficient cells up-regulate IL-1 signaling and overexpress IL-36α, a cytokine that is emerging as an important mediator of skin inflammation. These abnormal immune profiles were recapitulated by pharmacological inhibition of autophagy and verified in patient keratinocytes, where they were reversed by IL-36 blockade. These findings show that keratinocytes play a key role in skin autoinflammation and identify autophagy modulation of IL-36 signaling as a therapeutic target.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.