ArticleThe Journal of clinical investigation2022
Translational implications of Th17-skewed inflammation due to genetic deficiency of a cadherin stress sensor.
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 31 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 56 citations in OpenAlex.
- Plakophilin 1 suppresses keratinocyte innate immune responses through DExD/H helicases.Cellular & molecular immunology · 2026Article
- Interleukin 4-driven loss of stromal LIF signaling affects immune responses and cell-cell adhesion in atopic dermatitis.iScience · 2026Article
- Luteolin Disrupts Keratinocyte-Dendritic Cell Communication in Psoriasis by Targeting Rh Family C Glycoprotein.Mediators of inflammation · 2026Article
- Efficacy of interleukin-12/23 and interleukin-23 inhibitors in Hailey-Hailey disease.JAAD case reports · 2025Article
- Efficient On-Column Removal of Endotoxin from Immunoglobulins Such as AK23.Current protocols · 2025Article
- Exogenous ephrin-A3 reverses loss of vaginal epithelial barrier protection in progestin-treated mice.Mucosal immunology · 2025Article
- Crosstalk in Skin: Loss of Desmoglein 1 in Keratinocytes Inhibits BRAFThe Journal of investigative dermatology · 2025Article
- Desmosome mutations impact the tumor microenvironment to promote melanoma proliferation.Nature genetics · 2025Article
- Esophageal epithelial Ikkβ deletion promotes eosinophilic esophagitis in experimental allergy mouse model.The Journal of allergy and clinical immunology · 2025Article
- Meeting report - Alpine desmosome disease meeting 2024: advances and emerging topics in desmosomes and related diseases.Journal of cell science · 2025Article
- Ephrin-Eph signaling: an important regulator of epithelial integrity and barrier function.Tissue barriers · 2025Review
- BECLIN-1/BECN1 at the barrier: a gatekeeper of epithelial and endothelial homeostasis.Autophagy reports · 2025Review
- Dangerous liaisons: Loss of keratinocyte control over melanocytes in melanomagenesis.BioEssays : news and reviews in molecular, cellular and developmental biology · 2024Review
- Contribution of Keratinocytes in Skin Cancer Initiation and Progression.International journal of molecular sciences · 2024Review
- Desmosomes at a glance.Journal of cell science · 2024Review
- Immune Assessment Today: Optimizing and Standardizing Efforts to Monitor Immune Responses in Cancer and Beyond.Cancers · 2024Article
- Skin barrier-inflammatory pathway is a driver of the psoriasis-atopic dermatitis transition.Frontiers in medicine · 2024Review
- Melanoma cells repress Desmoglein 1 in keratinocytes to promote tumor cell migration.The Journal of cell biology · 2023Article
- Transcriptional profiling of rare acantholytic disorders suggests common mechanisms of pathogenesis.JCI insight · 2023Article
- Proteomic and Metabolomic Changes in Psoriasis Preclinical and Clinical Aspects.International journal of molecular sciences · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
26 authors at 6 institutions in 3 countries.
Funding
Abstract
Desmoglein 1 (Dsg1) is a cadherin restricted to stratified tissues of terrestrial vertebrates, which serve as essential physical and immune barriers. Dsg1 loss-of-function mutations in humans result in skin lesions and multiple allergies, and isolated patient keratinocytes exhibit increased proallergic cytokine expression. However, the mechanism by which genetic deficiency of Dsg1 causes chronic inflammation is unknown. To determine the systemic response to Dsg1 loss, we deleted the 3 tandem Dsg1 genes in mice. Whole transcriptome analysis of embryonic Dsg1-/- skin showed a delay in expression of adhesion/differentiation/keratinization genes at E17.5, a subset of which recovered or increased by E18.5. Comparing epidermal transcriptomes from Dsg1-deficient mice and humans revealed a shared IL-17-skewed inflammatory signature. Although the impaired intercellular adhesion observed in Dsg1-/- mice resembles that resulting from anti-Dsg1 pemphigus foliaceus antibodies, pemphigus skin lesions exhibit a weaker IL-17 signature. Consistent with the clinical importance of these findings, treatment of 2 Dsg1-deficient patients with an IL-12/IL-23 antagonist originally developed for psoriasis resulted in improvement of skin lesions. Thus, beyond impairing the physical barrier, loss of Dsg1 function through gene mutation results in a psoriatic-like inflammatory signature before birth, and treatment with a targeted therapy significantly improved skin lesions in patients.
Indexed as
Identifiers
What OpenQuestion holds
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.