ArticleThe Journal of clinical investigation2022
Congenital deficiency reveals critical role of ISG15 in skin homeostasis.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Fibroblasts in Scar Formation: Biology and Clinical Translation.Oxidative medicine and cellular longevity · 2022Pooled it
- Mechanistic insights into phage dynamics to overcome intracellular bacterial reservoirs in urinary tract infections.Npj viruses · 2026Article
- ISG15 negatively regulates RIPK3-mediated cell death and viral pathogenesis.Cell reports · 2026Article
- Human ISG15 deficiency unveils impaired healing of ulcerations via type I interferon-mediated fibrosis.Journal of human immunity · 2026Article
- When ISG15 is involved in inflammation.Frontiers in immunology · 2026Review
- A novel stop-loss variant in ISG15 causes C-terminal dysfunction and impairs USP18-mediated negative feedback.Frontiers in immunology · 2026Article
- Mitochondrial checkpoint for interferon responses in macrophages.Exploration of targeted anti-tumor therapy · 2026Review
- Ubiquitin-like Proteins in Autoimmune Diseases: Current Evidence and Therapeutic Opportunities.Immune network · 2025Review
- Identifying differentiation markers between dermal fibroblasts and adipose-derived mesenchymal stromal cells (AD-MSCs) in human visceral and subcutaneous tissues using single-cell transcriptomics.Stem cell research & therapy · 2025Article
- Sustained release of ubiquitin-like protein ISG-15 enhances tendon-to-bone healing following anterior cruciate ligament reconstruction in a mouse model.Frontiers in bioengineering and biotechnology · 2025Article
- Molecular mechanism of hypoxia and alpha-ketoglutaric acid on collagen expression in scleral fibroblasts.International journal of ophthalmology · 2024Article
- Elevated phospholipids and acylcarnitines C4 and C5 in cerebrospinal fluid distinguish viral CNS infections from autoimmune neuroinflammation.Journal of translational medicine · 2023Article
- Therapeutic Effects of Upadacitinib on Experimental Autoimmune Uveitis: Insights From Single-Cell Analysis.Investigative ophthalmology & visual science · 2023Article
- Case Report: ISG15 deficiency caused by novel variants in two families and effective treatment with Janus kinase inhibition.Frontiers in immunology · 2023Article
- Article
- ISG15 deficiency features a complex cellular phenotype that responds to treatment with itaconate and derivatives.Clinical and translational medicine · 2022Article
- Novel acetamide derivatives of 2-aminobenzimidazole prevent inflammatory arthritis in rats via suppression of pro-inflammatory mediators.Inflammopharmacology · 2022Article
- ISG15 and ISGylation in Human Diseases.Cells · 2022Review
- Ufl1 deficiency causes skin pigmentation by up-regulation of Endothelin-1.Frontiers in cell and developmental biology · 2022Article
Corrections and comments
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Authors and funding
21 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ulcerating skin lesions are manifestations of human ISG15 deficiency, a type I interferonopathy. However, chronic inflammation may not be their exclusive cause. We describe two siblings with recurrent skin ulcers that healed with scar formation upon corticosteroid treatment. Both had a homozygous nonsense mutation in the ISG15 gene, leading to unstable ISG15 protein lacking the functional domain. We characterized ISG15-/- dermal fibroblasts, HaCaT keratinocytes, and human induced pluripotent stem cell-derived vascular endothelial cells. ISG15-deficient cells exhibited the expected hyperinflammatory phenotype, but also dysregulated expression of molecules critical for connective tissue and epidermis integrity, including reduced collagens and adhesion molecules, but increased matrix metalloproteinases. ISG15-/- fibroblasts exhibited elevated ROS levels and reduced ROS scavenger expression. As opposed to hyperinflammation, defective collagen and integrin synthesis was not rescued by conjugation-deficient ISG15. Cell migration was retarded in ISG15-/- fibroblasts and HaCaT keratinocytes, but normalized under ruxolitinib treatment. Desmosome density was reduced in an ISG15-/- 3D epidermis model. Additionally, there were loose architecture and reduced collagen and desmoglein expression, which could be reversed by treatment with ruxolitinib/doxycycline/TGF-β1. These results reveal critical roles of ISG15 in maintaining cell migration and epidermis and connective tissue homeostasis, whereby the latter likely requires its conjugation to yet unidentified targets.
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Registered trials
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