ArticleThe Journal of clinical investigation2020
3D model of harlequin ichthyosis reveals inflammatory therapeutic targets.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- Altered skin microbiome, inflammation, and JAK/STAT signaling in Southeast Asian ichthyosis patients.Human genomics · 2024Pooled it
- An integrated design strategy for structurally stable full-thickness human skin models with regulatory-qualified barrier assessment.Materials today. Bio · 2026Article
- Dermal papillary fibroblasts promote persistent granulation tissue formation in junctional epidermolysis bullosa.EMBO molecular medicine · 2026Article
- Multiomics analysis reveals dermokine as a regulator of keratinocyte differentiation and adhesion.JCI insight · 2026Article
- Self-Assembled Skin Equivalents with Monoclonal CRISPR/Cas9-Modified N/TERT-1 Keratinocytes: A Cutting-Edge Model for Human Skin and its Diseases.Advanced healthcare materials · 2026Article
- Potential of 3D Skin Models and N/TERT-2G Cell Line in Genetic Research on Autosomal Recessive Nonsyndromic Epidermal Differentiation Disorders.Experimental dermatology · 2026Article
- Dysregulated cholesterol metabolism in genodermatoses: implications for systemic disease and therapeutic strategies.Frontiers in cell and developmental biology · 2026Review
- Genetic Engineering of Human Keratinocytes Using CRISPR/Cas9 Ribonucleoprotein Complexes or Modified Cas9-Encoding mRNAs.Methods in molecular biology (Clifton, N.J.) · 2026Article
- In Vitro Skin Models as Non-Animal Methods for Dermal Drug Development and Safety Assessment.Pharmaceutics · 2025Review
- Early Neonatal Death in Harlequin Ichthyosis: A Case Report and Literature Review.Clinical case reports · 2025Article
- Development of Human Skin Equivalents with Inducible Ceramide Depletion for In Vitro Modeling of Lipid Impairment.JID innovations : skin science from molecules to population health · 2025Article
- Development of pathological skin models: from conventional techniques to 3D bioprinting.Frontiers in bioengineering and biotechnology · 2025Review
- Hair follicles modulate skin barrier function.Cell reports · 2024Article
- Local and Sustained Baricitinib Delivery to the Skin through Injectable Hydrogels Containing Reversible Thioimidate Adducts.Advanced healthcare materials · 2024Article
- Hair follicles modulate skin barrier function.bioRxiv : the preprint server for biology · 2024Article
- Efficient Generation of CRISPR/Cas9-Mediated Knockout Human Primary Keratinocytes by Electroporation.Methods in molecular biology (Clifton, N.J.) · 2024Article
- A Review of CRISPR-Based Advances in Dermatological Diseases.Molecular diagnosis & therapy · 2023Review
- Ichthyosis linked to sphingosine 1-phosphate lyase insufficiency is due to aberrant sphingolipid and calcium regulation.Journal of lipid research · 2023Article
- Mutational Spectrum of theGenes · 2023Article
- Congenital Ichthyosis: A Practical Clinical Guide on Current Treatments and Future Perspectives.Clinical, cosmetic and investigational dermatology · 2023Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
The biology of harlequin ichthyosis (HI), a devastating skin disorder caused by loss-of-function mutations in the gene ABCA12, is poorly understood, and to date, no satisfactory treatment has been developed. We sought to investigate pathomechanisms of HI that could lead to the identification of new treatments for improving patients' quality of life. In this study, RNA-Seq and functional assays were performed to define the effects of loss of ABCA12 using HI patient skin samples and an engineered CRISPR/Cas9 ABCA12 KO cell line. The HI living skin equivalent (3D model) recapitulated the HI skin phenotype. The cytokines IL-36α and IL-36γ were upregulated in HI skin, whereas the innate immune inhibitor IL-37 was strongly downregulated. We also identified STAT1 and its downstream target inducible nitric oxide synthase (NOS2) as being upregulated in the in vitro HI 3D model and HI patient skin samples. Inhibition of NOS2 using the inhibitor 1400W or the JAK inhibitor tofacitinib dramatically improved the in vitro HI phenotype by restoring the lipid barrier in the HI 3D model. Our study has identified dysregulated pathways in HI skin that are feasible therapeutic targets.
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Registered trials
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.