ArticleNature immunology2010
Integrin CD11b negatively regulates TLR-triggered inflammatory responses by activating Syk and promoting degradation of MyD88 and TRIF via Cbl-b.
Article in Nature immunology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 277 papers.
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Who cites it
277 citing papers in PubMed, 452 citations in OpenAlex.
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- Preemptive cardioprotection with a small molecule in rodents that suppresses genes predictive of heart failure.Science advances · 2026Article
- Shared immune-inflammatory gene networks and drug prediction in polycystic ovary syndrome and type 2 diabetes mellitus: a bioinformatics and experimental validation study.Frontiers in endocrinology · 2026Article
- From mechanosensing to immune regulation: mechanisms of acupuncture signal initiation and amplification mediated by macrophages.Frontiers in immunology · 2026Review
- Proteomic and morphologic characterization of ovine macrophage differentiation and polarization.Scientific reports · 2025Article
- The integrin protein ITGβ1 effectively suppresses porcine epidemic diarrhea virus replication through facilitating MDA5 oligomerization and subsequent activation of the type I interferon signaling pathway.Journal of virology · 2025Article
- Matrix molecules associated with both regulation of inflammation and pathogenic outcomes associated with the surface of the lens in the eyes of EAU mice.Experimental eye research · 2025Article
- The HCMV tegument protein UL88 degrades MyD88 and reduces innate immune activation.Journal of virology · 2025Article
- CD11b Activation Reduces Myeloid Brain Infiltration and Mitigates Synucleinopathy in a Model of Parkinson's Disease.bioRxiv : the preprint server for biology · 2025Article
- The Roles of E3 Ubiquitin Ligases in Cerebral Ischemia-Reperfusion Injury.International journal of molecular sciences · 2025Review
- Macrophages as Multifaceted Orchestrators of Tissue Repair: Bridging Inflammation, Regeneration, and Therapeutic Innovation.Journal of inflammation research · 2025Review
- Integrin β2 regulates titanium particle‑induced inflammation in macrophages:Molecular medicine reports · 2025Article
- Fibrinogen and Neuroinflammation in the Neurovascular Unit in Stroke.Journal of inflammation research · 2025Review
- Elucidating the immunomodulatory roles and mechanisms of CUL4B in the immune system: a comprehensive review.Frontiers in immunology · 2025Review
- Cbl promotes MyD88 ubiquitin-mediated degradation in macrophages via phosphorylation and calcium mobilization.Frontiers in immunology · 2025Article
- Sustained STING-IRF7 signaling aggravates LPS-induced endometrial inflammation via excessive neutrophil extracellular traps generation.Frontiers in immunology · 2025Article
- β2-integrins as biomarkers in urothelial cancer.PloS one · 2025Article
- Ubiquitination in macrophage plasticity: from inflammatory to immunometabolic pathways.Frontiers in immunology · 2025Review
217 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Integrins are critical for the migration and function of leukocytes in inflammation. However, the interaction between integrin alpha(M) (CD11b), which has high expression in monocytes and macrophages, and Toll-like receptor (TLR)-triggered innate immunity remains unclear. Here we report that CD11b deficiency enhanced TLR-mediated responses in macrophages, rendering mice more susceptible to endotoxin shock and Escherichia coli-caused sepsis. CD11b was activated by TLR-triggered phosphatidylinositol 3-OH kinase (PI(3)K) and the effector RapL and fed back to inhibit TLR signaling by activating the tyrosine kinases Src and Syk. Syk interacted with and induced tyrosine phosphorylation of MyD88 and TRIF, which led to degradation of these adaptor molecules by the E3 ubiquitin ligase Cbl-b. Thus, TLR-triggered, active CD11b integrin engages in crosstalk with the MyD88 and TRIF pathways and subsequently inhibits TLR signaling in innate immune responses.
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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.