ArticleThe Journal of investigative dermatology2023
In Silico and In Vitro Analysis of IL36RN Alterations Reveals Critical Residues for the Function of the Interleukin-36 Receptor Complex.
Article in The Journal of investigative dermatology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 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
4 citing papers in PubMed, 1 synthesis or guideline pooled it, 3 citations in OpenAlex.
- Epidemiological, Genetic, Clinical, and Treatment Differences of Generalized Pustular Psoriasis and Acrodermatitis Continua of Hallopeau Across Ethnicities: A Systematic Review.American journal of clinical dermatology · 2025Pooled it
- SAPHO syndrome and pustular skin diseases: shared inflammatory circuits, divergent tissue outcomes, and the limits of a spectrum model.Frontiers in immunology · 2026Review
- Repurposing FDA-approved drugs for combating tigecycline resistance in Acinetobacter baumannii: in silico screening against BaeR protein.Molecular diversity · 2025Article
- Educational Case: Psoriasis.Academic pathologyArticle
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Generalized pustular psoriasis is a potentially life-threatening skin disease, associated with IL36RN disease alleles. IL36RN encodes the IL-36 receptor antagonist (IL-36Ra), a protein that downregulates the activity of IL-36 cytokines by blocking their receptor (IL-36R). Although generalized pustular psoriasis can be treated with IL-36R inhibitors, the structural underpinnings of the IL-36Ra/IL-36R interaction remain poorly understood. In this study, we sought to address this question by systematically investigating the effects of IL36RN sequence changes. We experimentally characterized the effects of 30 IL36RN variants on protein stability. In parallel, we used a machinelearning tool (Rhapsody) to analyze the IL-36Ra three-dimensional structure and predict the impact of all possible amino acid substitutions. This integrated approach identified 21 amino acids that are essential for IL-36Ra stability. We next investigated the effects of IL36RN changes on IL-36Ra/IL-36R binding and IL-36R signaling. Combining invitro assays and machine learning with a second program (mCSM), we identified 13 amino acids that are critical for IL-36Ra/IL36R engagement. Finally, we experimentally validated three representative predictions, further confirming the reliability of Rhapsody and mCSM. These findings shed light on the structural determinants of IL-36Ra activity, with potential to facilitate the design of new IL-36 inhibitors and aid the interpretation of IL36RN variants in diagnostic settings.
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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.