ReviewFrontiers in immunology2023
"Outside-to-inside," "inside-to-outside," and "intrinsic" endogenous pathogenic mechanisms in atopic dermatitis: keratinocytes as the key functional cells involved in both permeability barrier dysfunction and immunological alterations.
Review in Frontiers in immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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.
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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.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Keratinocytes as active regulators of cutaneous and mucosal immunity: a systematic review across inflammatory epithelial disorders.Frontiers in immunology · 2025Pooled it
- OX40 Ligand/OX40 Axis as the Inflammatory Prequel in Atopic Dermatitis: A Narrative Review.Dermatology and therapy · 2026Review
- Keratin gene expression signature predicts prognosis and immunotherapy efficacy in lung adenocarcinoma.Oncology letters · 2026Article
- Review
- Critical role of keratinocytes and protease-activated receptor 2 in secondary lymphedema development.Clinical and translational medicine · 2026Article
- Article
- Corticosteroid Phobia in Patients with Atopic Dermatitis: A Narrative Review.Clinical, cosmetic and investigational dermatology · 2026Review
- Factors Influencing Self-Management Behaviors in Patients with Atopic Dermatitis and Intervention Strategies: A Narrative Review.Patient preference and adherence · 2026Review
- Review
- Small EVs From Adipose-Derived MSCs Modulate Epidermal Barrier and Inflammation Via Sphingosine-1-Phosphate Signaling Pathway.Journal of extracellular vesicles · 2025Article
- Transcriptomic Profiling of Lesional and Perilesional Skin in Atopic Dermatitis Suggests Barrier Dysfunction, Inflammatory Activation, and Alterations to Vitamin D Metabolism.International journal of molecular sciences · 2025Article
- Article
- HSPA2 influences the differentiation and production of immunomodulatory mediators in human immortalized epidermal keratinocyte lines.Cell death & disease · 2025Article
- Immunological Antagonism Between Psoriasis and Atopic Dermatitis: Pathways, Clinical Implications, and Therapeutic Perspectives.Clinical, cosmetic and investigational dermatology · 2025Review
- Role of skin-homing t-cells in recurrent episodes of atopic dermatitis: a review.Frontiers in immunology · 2025Review
- Review of sensory systems deployed by epidermal keratinocytes.Frontiers in cell and developmental biology · 2025Review
- A murine model of prurigo nodularis-like skin lesions induced by persistent scratching under type 2 inflammatory conditions.Frontiers in immunology · 2025Article
- The therapeutic potential ofFrontiers in pharmacology · 2025Review
- Exploring novel drug targets for atopic dermatitis through plasma proteome with genome.Archives of dermatological research · 2024Article
- Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Permeability barrier disruption has been shown to induce immunological alterations (i.e., an "outside-to-inside" pathogenic mechanism). Conversely, several inflammatory and immunological mechanisms reportedly interrupt permeability barrier homeostasis (i.e., an "inside-to-outside" pathogenic mechanism). It is now widely recognized that alterations of even a single molecule in keratinocytes can lead to not only permeability barrier dysfunction but also to immunological alterations. Such a simultaneous, bidirectional functional change by keratinocytes is herein named an "intrinsic" pathogenic mechanism. Molecules and/or pathways involved in this mechanism could be important not only as factors in disease pathogenesis but also as potential therapeutic targets for inflammatory cutaneous diseases, such as atopic dermatitis, psoriasis, and prurigo nodularis. Elevation of skin surface pH following permeability barrier abrogation comprises one of the key pathogenic phenomena of the "outside-to-inside" mechanism. Not only type 2 cytokines (e.g., IL-4, IL-13, IL-31) but also type 1 (e.g. IFN-γ), and type 3 (e.g., IL-17, IL-22) as well as several other inflammatory factors (e.g. histamine) can disrupt permeability barrier homeostasis and are all considered part of the "inside-to-outside" mechanism. Finally, examples of molecules relevant to the "intrinsic" pathogenic mechanism include keratin 1, filaggrin, and peroxisome proliferator-activated receptor-α (PPARα).
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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.