ArticleThe Journal of clinical investigation2010
Elastase 2 is expressed in human and mouse epidermis and impairs skin barrier function in Netherton syndrome through filaggrin and lipid misprocessing.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 128 citations in OpenAlex.
- Outcomes of Systemic Treatment in Children and Adults With Netherton Syndrome: A Systematic Review.Frontiers in immunology · 2022Pooled it
- Evaluation of filaggrin 2 expression in dogs with atopic dermatitis before and after oclacitinib maleate administration.Veterinary dermatology · 2025Article
- Developing a Core Outcome Set for Netherton Syndrome: An International Multi-Stakeholder e-Delphi Consensus Study.Dermatology (Basel, Switzerland) · 2025Article
- Interleukin-36 Is Highly Expressed in Skin Biopsies from Two Patients with Netherton Syndrome.Dermatopathology (Basel, Switzerland) · 2024Article
- Interleukin-13 Inhibitors in the Treatment of Atopic Dermatitis: The Role of Tralokinumab.Dermatology practical & conceptual · 2024Review
- Comparative analyses of Netherton syndrome patients and Spink5 conditional knock-out mice uncover disease-relevant pathways.Communications biology · 2024Article
- Protease-Activated Receptor 2 in inflammatory skin disease: current evidence and future perspectives.Frontiers in immunology · 2024Review
- Proteomic profiling of sweat in patients with cystic fibrosis provides new insights into epidermal homoeostasis.Skin health and disease · 2023Article
- Article
- Revisiting the Roles of Filaggrin in Atopic Dermatitis.International journal of molecular sciences · 2022Review
- Epithelial production of elastase is increased in inflammatory bowel disease and causes mucosal inflammation.Mucosal immunology · 2021Article
- Phenotype-genotype comorbidity analysis of patients with rare disorders provides insight into their pathological and molecular bases.PLoS genetics · 2020Article
- Efficient CRISPR-Cas9-Mediated Gene Ablation in Human Keratinocytes to Recapitulate Genodermatoses: Modeling of Netherton Syndrome.Molecular therapy. Methods & clinical development · 2020Article
- Comel-Netherton syndrome: A local skin barrier defect in the absence of an underlying systemic immunodeficiency.Allergy · 2020Article
- Skin barrier lipid enzyme activity in Netherton patients is associated with protease activity and ceramide abnormalities.Journal of lipid research · 2020Article
- Genetic activation of Nrf2 reduces cutaneous symptoms in a murine model of Netherton syndrome.Disease models & mechanisms · 2020Article
- Kallikreins: Essential epidermal messengers for regulation of the skin microenvironment during homeostasis, repair and disease.Matrix biology plus · 2020Article
- Liquid-liquid phase separation drives skin barrier formation.Science (New York, N.Y.) · 2020Article
- Interplay of Staphylococcal and Host Proteases Promotes Skin Barrier Disruption in Netherton Syndrome.Cell reports · 2020Article
- Protease-Activated Receptor-2 Regulates Neuro-Epidermal Communication in Atopic Dermatitis.Frontiers in immunology · 2020Article
Corrections and comments
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Authors and funding
12 authors at 7 institutions in 2 countries.
Funding
Abstract
The human epidermis serves 2 crucial barrier functions: it protects against water loss and prevents penetration of infectious agents and allergens. The physiology of the epidermis is maintained by a balance of protease and antiprotease activities, as illustrated by the rare genetic skin disease Netherton syndrome (NS), in which impaired inhibition of serine proteases causes severe skin erythema and scaling. Here, utilizing mass spectrometry, we have identified elastase 2 (ELA2), which we believe to be a new epidermal protease that is specifically expressed in the most differentiated layer of living human and mouse epidermis. ELA2 localized to keratohyalin granules, where it was found to directly participate in (pro-)filaggrin processing. Consistent with the observation that ELA2 was hyperactive in skin from NS patients, transgenic mice overexpressing ELA2 in the granular layer of the epidermis displayed abnormal (pro-)filaggrin processing and impaired lipid lamellae structure, which are both observed in NS patients. These anomalies led to dehydration, implicating ELA2 in the skin barrier defect seen in NS patients. Thus, our work identifies ELA2 as a major new epidermal protease involved in essential pathways for skin barrier function. These results highlight the importance of the control of epidermal protease activity in skin homeostasis and designate ELA2 as a major protease driving the pathogenesis of NS.
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