ArticleGut2020
IL23 induces IL23R recycling and amplifies innate receptor-induced signalling and cytokines in human macrophages, and the IBD-protective IL23R R381Q variant modulates these outcomes.
Article in Gut, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 55 citations in OpenAlex.
- Interleukin-39 aggravates sepsis by inducing self-sustaining neutrophil activation in the lungs via the CXCL1-CXCR2 pathway.International journal of biological sciences · 2026Article
- The Evolutionary Trajectory and Prognostic Value of GITR+ Tregs Reprogramed by Tumor-Intrinsic PD-1/c-MET Signaling in Pancreatic Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Interleukin 23: Pathogenetic Involvement and Therapeutic Target for Ulcerative Colitis.Journal of clinical medicine · 2025Review
- Targeting the IL-23 Receptor Gene: A Promising Approach in Inflammatory Bowel Disease Treatment.International journal of molecular sciences · 2025Review
- Charge-based immunoreceptor signalling in health and disease.Nature reviews. Immunology · 2025Review
- Article
- The mode of action of IL-23 in experimental inflammatory arthritic pain and disease.Arthritis research & therapy · 2024Article
- Intestinal CXCR6Immunity · 2024Article
- Thymopentapeptide Affects T-Cell Subsets by Modulating the Flora of the Skin Surface to Alleviate Psoriasis.Drug design, development and therapy · 2024Article
- IL-12 and IL-23 pathway inhibition in inflammatory bowel disease.Nature reviews. Gastroenterology & hepatology · 2023Review
- The NLRP3 inflammasome: contributions to inflammation-related diseases.Cellular & molecular biology letters · 2023Review
- The Role of IL-23 in the Pathogenesis and Therapy of Inflammatory Bowel Disease.International journal of molecular sciences · 2023Review
- Use of NanoBiT and NanoBRET to characterise interleukin-23 receptor dimer formation in living cells.British journal of pharmacology · 2023Article
- Longitudinal DNA methylation profiling of the rectal mucosa identifies cell-specific signatures of disease status, severity and clinical outcomes in ulcerative colitis cell-specific DNA methylation signatures of UC.Clinical epigenetics · 2023Article
- Review
- Pseudomonas Aeruginosa Lung Infection Subverts Lymphocytic Responses through IL-23 and IL-22 Post-Transcriptional Regulation.International journal of molecular sciences · 2022Article
- Interleukin-23 in the Pathogenesis of Inflammatory Bowel Disease and Implications for Therapeutic Intervention.Journal of Crohn's & colitis · 2022Review
- Transcriptome Revealed Exposure to the Environmental Ammonia Induced Oxidative Stress and Inflammatory Injury in Spleen of Fattening Pigs.Animals : an open access journal from MDPI · 2022Article
- Pattern Recognition Receptor Signaling and Cytokine Networks in Microbial Defenses and Regulation of Intestinal Barriers: Implications for Inflammatory Bowel Disease.Gastroenterology · 2022Review
- Intestinal immune compartmentalization: implications of tissue specific determinants in health and disease.Mucosal immunology · 2021Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
objectiveThe interleukin (IL)23 pathway contributes to IBD pathogenesis and is being actively studied as a therapeutic target in patients with IBD. Unexpected outcomes in these therapeutic trials have highlighted the importance of understanding the cell types and mechanisms through which IL23 regulates immune outcomes. How IL23 regulates macrophage outcomes and the consequences of the IL23R R381Q IBD-protective variant on macrophages are not well defined; macrophages are key players in IBD pathogenesis and inflammation.
designWe analysed protein and RNA expression, signalling and localisation in human monocyte-derived macrophages (MDMs) through western blot, ELISA, real-time PCR, flow cytometry, immunoprecipitation and microscopy.
resultsIL23R was critical for optimal levels of pattern-recognition receptor (PRR)-induced signalling and cytokines in human MDMs. In contrast to the coreceptor IL12Rβ1, IL23 induced dynamic IL23R cell surface regulation and this required clathrin and dynamin-mediated endocytosis and endocytic recycling-dependent pathways; these pathways were essential for IL23R-mediated outcomes. The IBD-protective IL23R R381Q variant showed distinct outcomes. Relative to IL23R R381, HeLa cells expressing IL23R Q381 showed decreased IL23R recycling and reduced assembly of IL23R Q381 with Janus kinase/signal transducer and activator of transcription pathway members. In MDMs from IL23R Q381 carriers, IL23R accumulated in late endosomes and lysosomes on IL23 treatment and cells demonstrated decreased IL23R- and PRR-induced signalling and cytokines relative to IL23R R381 MDMs.
conclusionMacrophage-mediated inflammatory pathways are key contributors to IBD pathogenesis, and we identify an autocrine/paracrine IL23 requirement in PRR-initiated human macrophage outcomes and in human intestinal myeloid cells, establish that IL23R undergoes ligand-induced recycling, define mechanisms regulating IL23R-induced signalling and determine how the IBD-protective IL23R R381Q variant modulates these processes.
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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.