Trial reportJournal of immunology (Baltimore, Md. : 1950)2014
The IL18RAP region disease polymorphism decreases IL-18RAP/IL-18R1/IL-1R1 expression and signaling through innate receptor-initiated pathways.
Trial report in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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
41 citing papers in PubMed, 61 citations in OpenAlex.
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- Multi-omics integrated approach reveals host-microbiome interactions in the adaptive mechanisms of weaning piglets.Journal of animal science and technology · 2026Article
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- Profiling genetically driven alternative splicing across the Indonesian archipelago.American journal of human genetics · 2024Article
- LRRK2 G2019S Promotes Colon Cancer Potentially via LRRK2-GSDMD Axis-Mediated Gut Inflammation.Cells · 2024Article
- The relationship between extreme inter-individual variation in macrophage gene expression and genetic susceptibility to inflammatory bowel disease.Human genetics · 2024Article
- Host-microbe interactions in the nasal cavity of dogs with chronic idiopathic rhinitis.Frontiers in veterinary science · 2024Article
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- The Diagnostic Features of Peripheral Blood Biomarkers in Identifying Osteoarthritis Individuals: Machine Learning Strategies and Clinical Evidence.Current computer-aided drug design · 2024Article
- Modulation of intestinal IL-37 expression and its impact on the epithelial innate immune response and barrier integrity.Frontiers in immunology · 2023Article
- Key Genes Associated with Tumor-Infiltrating Non-regulatory CD4- and CD8-Positive T Cells in Microenvironment of Hepatocellular Carcinoma.Biochemical genetics · 2022Article
- Selective Targeting of Tumour Necrosis Factor Receptor 1 Induces Stable Protection from Crohn's-Like Ileitis in TNFΔARE Mice.Journal of Crohn's & colitis · 2022Article
- Pattern Recognition Receptor Signaling and Cytokine Networks in Microbial Defenses and Regulation of Intestinal Barriers: Implications for Inflammatory Bowel Disease.Gastroenterology · 2022Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Fine-tuning of cytokine-inducing pathways is essential for immune homeostasis. Consistently, a dysregulated increase or decrease in pattern-recognition receptor (PRR)-induced signaling and cytokine secretion can lead to inflammatory bowel disease. Multiple gene loci are associated with inflammatory bowel disease, but their functional effects are largely unknown. One such region in chromosome 2q12 (rs917997), also associated with other immune-mediated diseases, encompasses IL18RAP. We found that human monocyte-derived macrophages (MDMs) from rs917997 AA risk carriers secrete significantly less cytokines than G carriers upon stimulation of multiple PRRs, including nucleotide-binding oligomerization domain 2 (NOD2). We identified that IL-18 signaling through IL-18RAP was critical in amplifying PRR-induced cytokine secretion in MDMs. IL-18RAP responded to NOD2-initiated early, caspase-1-dependent autocrine IL-18, which dramatically enhanced MAPK, NF-κB, PI3K, and calcium signaling. Reconstituting MAPK activation was sufficient to rescue decreased cytokines in NOD2-stimulated IL-18RAP-deficient MDMs. Relative to GG carriers, MDM from rs917997 AA carriers had decreased expression of cell-surface IL-18RAP protein, as well as of IL-18R1 and IL-1R1, genes also located in the IL18RAP region. Accordingly, these risk-carrier MDMs show diminished PRR-, IL-18-, and IL-1-induced MAPK and NF-κB signaling. Taken together, our results demonstrate clear functional consequences of the rs917997 risk polymorphism; this polymorphism leads to a loss-of-function through decreased IL-18RAP, IL-18R1, and IL-1R1 protein expression, which impairs autocrine IL-18 and IL-1 signaling, thereby leading to decreased cytokine secretion in MDMs upon stimulation of a broad range of PRRs.
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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.