ArticleThe Journal of experimental medicine2014
Transgenic kallikrein 5 mice reproduce major cutaneous and systemic hallmarks of Netherton syndrome.
Article in The Journal of experimental medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 103 citations in OpenAlex.
- IL-13 and calpain-14 suppress the expression of SPINK7 by regulating OVOL1 in eosinophilic esophagitis.JCI insight · 2026Article
- Critical role of keratinocytes and protease-activated receptor 2 in secondary lymphedema development.Clinical and translational medicine · 2026Article
- Dysregulated proteolytic cascades in Netherton syndrome: from molecular pathology to preclinical drug testing.The Journal of pathology · 2026Review
- Cytokine Milieu Relevant to Atopic Dermatitis Enhances Epidermal Trypsin-Like Serine Protease Activity, Which Is Pharmacologically Suppressed in Human Keratinocytes.The Journal of dermatology · 2026Article
- Luteolin Disrupts Keratinocyte-Dendritic Cell Communication in Psoriasis by Targeting Rh Family C Glycoprotein.Mediators of inflammation · 2026Article
- KLK5 and KLK7 drive cervical carcinoma via KLK14-dependent RhoA and NF-κB pathways.Translational oncology · 2025Article
- Comparative analysis of cutaneous features of psoriasis in acute and chronic imiquimod-induced mouse models.Scientific reports · 2025Article
- Comparative analyses of Netherton syndrome patients and Spink5 conditional knock-out mice uncover disease-relevant pathways.Communications biology · 2024Article
- An update on mechanisms of pruritus and their potential treatment in primary cutaneous T-cell lymphoma.Clinical and experimental medicine · 2023Review
- Type I IFNs link skin-associated dysbiotic commensal bacteria to pathogenic inflammation and angiogenesis in rosacea.JCI insight · 2023Article
- Treatment Experiences with Intravenous Immunoglobulins, Ixekizumab, Dupilumab, and Anakinra in Netherton Syndrome: A Case Series.Dermatology (Basel, Switzerland) · 2023Article
- Transcriptomic Analysis of the Major Orphan Ichthyosis Subtypes Reveals Shared Immune and Barrier Signatures.The Journal of investigative dermatology · 2022Article
- Loricrin at the Boundary between Inside and Outside.Biomolecules · 2022Review
- A novel mutation inFrontiers in genetics · 2022Article
- The Epidermis: Redox Governor of Health and Diseases.Antioxidants (Basel, Switzerland) · 2021Review
- A Suite of Activity-Based Probes To Dissect the KLK Activome in Drug-Resistant Prostate Cancer.Journal of the American Chemical Society · 2021Article
- Human Tissue Kallikreins-Related Peptidases Are Targets for the Treatment of Skin Desquamation Diseases.Frontiers in medicine · 2021Review
- Kallikrein 7 Promotes Atopic Dermatitis-Associated Itch Independently of Skin Inflammation.The Journal of investigative dermatology · 2020Article
- Genetic activation of Nrf2 reduces cutaneous symptoms in a murine model of Netherton syndrome.Disease models & mechanisms · 2020Article
- Functional role of kallikrein 5 and proteinase-activated receptor 2 in eosinophilic esophagitis.Science translational medicine · 2020Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Netherton syndrome (NS) is a severe genetic skin disease in which absence of a key protease inhibitor causes congenital exfoliative erythroderma, eczematous-like lesions, and atopic manifestations. Several proteases are overactive in NS, including kallikrein-related peptidase (KLK) 5, KLK7, and elastase-2 (ELA2), which are suggested to be part of a proteolytic cascade initiated by KLK5. To address the role of KLK5 in NS, we have generated a new transgenic murine model expressing human KLK5 in the granular layer of the epidermis (Tg-KLK5). Transgene expression resulted in increased proteolytic activity attributable to KLK5 and its downstream targets KLK7, KLK14, and ELA2. Tg-KLK5 mice developed an exfoliative erythroderma with scaling, growth delay, and hair abnormalities. The skin barrier was defective and the stratum corneum was detached through desmosomal cleavage. Importantly, Tg-KLK5 mice displayed cutaneous and systemic hallmarks of severe inflammation and allergy with pruritus. The skin showed enhanced expression of inflammatory cytokines and chemokines, infiltration of immune cells, and markers of Th2/Th17/Th22 T cell responses. Moreover, serum IgE and Tslp levels were elevated. Our study identifies KLK5 as an important contributor to the NS proteolytic cascade and provides a new and viable model for the evaluation of future targeted therapies for NS or related diseases such as atopic dermatitis.
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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.