ArticleCellular and molecular gastroenterology and hepatology2020
IL23 Promotes Antimicrobial Pathways in Human Macrophages, Which Are Reduced With the IBD-Protective IL23R R381Q Variant.
Article in Cellular and molecular gastroenterology and hepatology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
- IL1βJournal of translational medicine · 2026Article
- Furamidine enhances IL-23-mediated autophagic response through IL-23R-TYK2-STAT3-dependent regulation of intracellular Ca²⁺ level to facilitate mycobacterial clearance in human macrophages.Medical microbiology and immunology · 2025Article
- The gut immune axis in ulcerative colitis: insights from microbiome research.Molecular biology reports · 2025Review
- Cardiotonic Steroids as a Potential Novel Approach for Immunomodulation in Inflammatory Bowel Disease.Journal of clinical medicine · 2025Review
- Charge-based immunoreceptor signalling in health and disease.Nature reviews. Immunology · 2025Review
- Age-dependent differences in type I interferon, IL-12 and pro-inflammatory cytokine production by porcine peripheral blood mononuclear cells in response to pseudorabies virus-infected cells.Frontiers in immunology · 2025Article
- Evolutionary insights into Interleukin-12 family targets across 405 species.Frontiers in immunology · 2025Article
- The IL-23R and Its Genetic Variants: A Hitherto Unforeseen Bridge Between the Immune System and Cancer Development.Cancers · 2024Review
- Human Amniotic MSC Response in LPS-Stimulated Ascites from Patients with Cirrhosis: FOXO1 Gene and Th17 Activation in Enhanced Antibacterial Activation.International journal of molecular sciences · 2024Article
- The Role of the Microbiome in the Pathogenesis and Treatment of Ulcerative Colitis-A Literature Review.Biomedicines · 2023Review
- Human MCTS1-dependent translation of JAK2 is essential for IFN-γ immunity to mycobacteria.Cell · 2023Article
- Review
- IL-12 and IL-23 pathway inhibition in inflammatory bowel disease.Nature reviews. Gastroenterology & hepatology · 2023Review
- Targeting macrophage autophagy for inflammation resolution and tissue repair in inflammatory bowel disease.Burns & trauma · 2023Review
- Management of Infections in Psoriatic Patients Treated with Systemic Therapies: A Lesson from the Immunopathogenesis of Psoriasis.Dermatology practical & conceptual · 2023Review
- Comparative functional analysis of macrophage phagocytosis in Dagu chickens and Wenchang chickens.Frontiers in immunology · 2023Article
- 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
- Autophagy impairment in liver CD11cNature communications · 2022Article
- Blocking the Notch signal transduction pathway promotes tumor growth in breast cancer by promoting the expression of suppressible inflammatory factors.Annals of translational medicine · 2022Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
BACKGROUND &
aimsInterleukin (IL)23 is a major contributor to inflammatory bowel disease (IBD) pathogenesis and is being pursued as a therapeutic target, both through targeting IL23 alone or in combination with IL12. Unexpected trial outcomes highlight the importance of understanding the cell types through which IL23 regulates immune responses, and how IL23 and IL12 compare in these responses. Macrophages are key players in IBD, and IL23 recently was found to promote inflammatory outcomes in human macrophages. This raises the possibility that IL23 may be required for additional essential macrophage functions, in particular microbial clearance, such that either blocking the IL23 pathway or the IL23R-R381Q IBD-protective variant may reduce macrophage-mediated microbial clearance.
methodsWe analyzed protein expression, signaling, bacterial uptake, and intracellular bacterial clearance in human monocyte-derived macrophages through Western blot, flow cytometry, and gentamicin protection.
resultsAutocrine/paracrine IL23 was critical for optimal levels of pattern-recognition-receptor (PRR)-induced intracellular bacterial clearance in human macrophages. Mechanisms regulated by IL23 included induction of pyruvate dehydrogenase kinase 1-dependent bacterial uptake, and up-regulation of reactive oxygen species through nicotinamide adenine dinucleotide phosphate oxidase members, nitric oxide synthase 2, and autophagy through ATG5 and ATG16L1. Complementing these pathways in IL23R-deficient macrophages restored PRR-induced bacterial uptake and clearance. Janus kinase 2, TYK2, and STAT3 were required for IL23-induced mechanisms. IL23 and IL12 induced antimicrobial pathways to similar levels in human macrophages. Relative to IL23R-R381, transfected IL23R-Q381, or monocyte-derived macrophages from IL23R-Q381 carriers showed reduced bacterial uptake and clearance.
conclusionsWe identify that autocrine/paracrine IL23 is required for optimal PRR-enhanced macrophage bacterial uptake and intracellular bacterial clearance, define mechanisms regulating IL23R-induced bacterial clearance, and determine how the IBD-protective IL23R-R381Q variant modulates these processes.
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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.