ArticleScientific reports2015
A novel crosstalk between TLR4- and NOD2-mediated signaling in the regulation of intestinal inflammation.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 45 citations in OpenAlex.
- Probing Immune Signatures of Conjugated Pattern Recognition Receptor Ligands Identifies Chimeras with Potent Adjuvant and Antitumor Activities.Journal of medicinal chemistry · 2026Article
- Sleep deprivation disrupts lacrimal gland homeostasis via hypothalamic-pituitary-adrenal axis and gut dysbiosis in mice.Communications biology · 2026Article
- Distinct colitis-associated macrophages drive NOD2-dependent bacterial sensing and gut homeostasis.The Journal of clinical investigation · 2025Article
- The immune system in cardiovascular diseases: from basic mechanisms to therapeutic implications.Signal transduction and targeted therapy · 2025Review
- A nod to paratuberculosis: NOD1 and NOD2 expression in the pathological spectrum ofFrontiers in veterinary science · 2025Article
- NOD2-mediated dual negative regulation of inflammatory responses triggered by TLRs in the gastrointestinal tract.Frontiers in immunology · 2024Review
- Mutanolysin-Digested Peptidoglycan ofInternational journal of molecular sciences · 2023Article
- Prophylactic vs. Therapeutic Effect of Probiotics on the Inflammation Mediated by the NF-κB Pathway in Inflammatory Bowel Conditions.Biomedicines · 2023Article
- Gram-Positive Bacteria Cell Wall Peptidoglycan Polymers Activate Human Dendritic Cells to Produce IL-23 and IL-1β and Promote TMicroorganisms · 2023Article
- Astaxanthin Alleviates Inflammatory Response in Neonatal Necrotizing Enterocolitis Rats by Regulating NOD2/TLR4 Pathway.Gastroenterology research and practice · 2023Article
- Anethole Attenuates EnterotoxigenicFrontiers in microbiology · 2021Article
- Higher PIK3C2B gene expression of H1N1+ specific B-cells is associated with lower H1N1 immunogenicity after trivalent influenza vaccination in HIV infected children.Clinical immunology (Orlando, Fla.) · 2020Article
- Whole-Genome DNA Methylation Profiling of CD14+ Monocytes Reveals Disease Status and Activity Differences in Crohn's Disease Patients.Journal of clinical medicine · 2020Article
- Novel ClinicalMicroorganisms · 2020Review
- Impact of Toll-Like Receptor 4 Signaling in Necrotizing Enterocolitis: The State of the Science.Clinics in perinatology · 2019Review
- The Nod2 Agonist Muramyl Dipeptide Cooperates with the TLR4 Agonist Lipopolysaccharide to Enhance IgG2b Production in Mouse B Cells.Journal of immunology research · 2019Article
- Multi-omic analysis of signalling factors in inflammatory comorbidities.BMC bioinformatics · 2018Article
- Human Breast-Milk Feeding Enhances the Humoral and Cell-Mediated Immune Response in Neonatal Piglets.The Journal of nutrition · 2018Article
- Glutamate alleviates intestinal injury, maintains mTOR and suppresses TLR4 and NOD signaling pathways in weanling pigs challenged with lipopolysaccharide.Scientific reports · 2018Article
- Glycine Relieves Intestinal Injury by Maintaining mTOR Signaling and Suppressing AMPK, TLR4, and NOD Signaling in Weaned Piglets after Lipopolysaccharide Challenge.International journal of molecular sciences · 2018Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although Toll-like receptor 4 (TLR4)- and nucleotide-binding oligomerization domain 2 (NOD2)-mediated signaling mechanisms have been extensively studied individually, the crosstalk between them in the regulation of intestinal mucosal defense and tissue homeostasis has been underappreciated. Here, we uncover some novel activities of NOD2 by gene expression profiling revealing the global nature of the cross-regulation between TLR4- and NOD2-mediated signaling. Specifically, NOD2 is able to sense the intensity of TLR4-mediated signaling, resulting in either synergistic stimulation of Interluekin-12 (IL-12) production when the TLR signaling intensity is low; or in the inhibition of IL-12 synthesis and maintenance of intestinal mucosal homeostasis when the TLR signaling intensifies. This balancing act is mediated through receptor-interacting serine/threonine kinase 2, and the transcriptional regulator CCAAT/enhancer-binding protein α (C/EBPα) via its serine 248 phosphorylation by Protein Kinase C. Mice deficient in C/EBPα in the hematopoietic compartment are highly susceptible to chemically induced experimental colitis in an IL-12-dependent manner. Additionally, in contrast to the dogma, we find that the major Crohn's disease-associated NOD2 mutations could cause a primarily immunodeficient phenotype by selectively impairing TLR4-mediated IL-12 production and host defense. To restore the impaired homeostasis would be a way forward to developing novel therapeutic strategies for inflammatory bowel diseases.
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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.