ArticlePLoS biology2008
Notch-deficient skin induces a lethal systemic B-lymphoproliferative disorder by secreting TSLP, a sentinel for epidermal integrity.
Article in PLoS biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers, 1 of them a synthesis that pooled it.
What it found
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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
113 citing papers in PubMed, 1 synthesis or guideline pooled it, 169 citations in OpenAlex.
- Serum thymic stromal lymphopoietin (TSLP) levels in atopic dermatitis patients: a systematic review and meta-analysis.Clinical and experimental medicine · 2023Pooled it
- Identifying dendritic cell heterogeneity and potential risk genes in atopic dermatitis: integrative scRNA-seq, bulk RNA-seq analyses and experimental validation.Frontiers in medicine · 2026Article
- Molecular and cellular dynamics of squamous cell carcinomas across tissues.Genes & development · 2025Review
- Notch signalling in T cells: bridging tumour immunity and intratumoral cellular crosstalk.Frontiers in immunology · 2025Review
- FGFR2 and NOTCH1 Expression Inversely Correlated in Progressive Cutaneous Carcinogenesis in an Experimental Mouse Model.Journal of personalized medicine · 2024Article
- Notch1 cortical signaling regulates epithelial architecture and cell-cell adhesion.The Journal of cell biology · 2023Article
- Notch1 cortical signaling regulates epithelial architecture and cell-cell adhesion.bioRxiv : the preprint server for biology · 2023Article
- The Role of TSLP in Atopic Dermatitis: From Pathogenetic Molecule to Therapeutical Target.Mediators of inflammation · 2023Review
- Anti-Itching and Anti-Inflammatory Effects of Kushenol F via the Inhibition of TSLP Production.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Epithelial barrier dysfunction in ocular allergy.Allergy · 2022Review
- Alarmin Cytokines as Central Regulators of Cutaneous Immunity.Frontiers in immunology · 2022Review
- Notch signaling in oral pre-cancer and oral cancer.Medical oncology (Northwood, London, England) · 2021Review
- Atopic dermatitis is associated with hidradenitis suppurativa diagnosis: A single institution retrospective cohort study.JAAD international · 2021Article
- Review
- Cancer Stem Cells,Cells · 2020Review
- The pathogenic role of innate lymphoid cells in autoimmune-related and inflammatory skin diseases.Cellular & molecular immunology · 2020Review
- Endocrine Disruptor Bisphenol A (BPA) Triggers Systemic Para-Inflammation and is Sufficient to Induce Airway Allergic Sensitization in Mice.Nutrients · 2020Article
- Cutaneous Effects of Notch Inhibitor Therapy: A Report of Two Cases.Case reports in dermatological medicine · 2020Article
- TSLP: from allergy to cancer.Nature immunology · 2019Review
- Tumor-Derived Thymic Stromal Lymphopoietin Expands Bone Marrow B-cell Precursors in Circulation to Support Metastasis.Cancer research · 2019Article
53 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Epidermal keratinocytes form a highly organized stratified epithelium and sustain a competent barrier function together with dermal and hematopoietic cells. The Notch signaling pathway is a critical regulator of epidermal integrity. Here, we show that keratinocyte-specific deletion of total Notch signaling triggered a severe systemic B-lymphoproliferative disorder, causing death. RBP-j is the DNA binding partner of Notch, but both RBP-j-dependent and independent Notch signaling were necessary for proper epidermal differentiation and lipid deposition. Loss of both pathways caused a persistent defect in skin differentiation/barrier formation. In response, high levels of thymic stromal lymphopoietin (TSLP) were released into systemic circulation by Notch-deficient keratinocytes that failed to differentiate, starting in utero. Exposure to high TSLP levels during neonatal hematopoiesis resulted in drastic expansion of peripheral pre- and immature B-lymphocytes, causing B-lymphoproliferative disorder associated with major organ infiltration and subsequent death, a previously unappreciated systemic effect of TSLP. These observations demonstrate that local skin perturbations can drive a lethal systemic disease and have important implications for a wide range of humoral and autoimmune diseases with skin manifestations.
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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.