ArticleThe Journal of clinical investigation2017
CD11b activation suppresses TLR-dependent inflammation and autoimmunity in systemic lupus erythematosus.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 109 citations in OpenAlex.
- Toll-like receptors in innate immunity and inflammation: from fundamental biology to clinic insights.Immunity & inflammation · 2026Review
- Proteomic and morphologic characterization of ovine macrophage differentiation and polarization.Scientific reports · 2025Article
- CD11b Activation Reduces Myeloid Brain Infiltration and Mitigates Synucleinopathy in a Model of Parkinson's Disease.bioRxiv : the preprint server for biology · 2025Article
- Age-Associated B Cells in Autoimmune Diseases: Pathogenesis and Clinical Implications.Clinical reviews in allergy & immunology · 2025Review
- DDIT3 deficiency ameliorates systemic lupus erythematosus by regulating B cell activation and differentiation.Life medicine · 2025Article
- Enhanced neoangiogenesis and balance of the immune response mediated by the Wilms' tumor suppressor WT1 favor repair after myocardial infarction.Theranostics · 2025Article
- TRIM21 regulation of IRF-mediated type I interferon signaling in systemic autoimmune diseases.Frontiers in immunology · 2025Review
- Unveiling macrophage dynamics and efferocytosis-related targets in diabetic kidney disease: insights from single-cell and bulk RNA-sequencing.Frontiers in immunology · 2025Article
- A proteogenomic analysis of cervical cancer reveals therapeutic and biological insights.Nature communications · 2024Article
- The multiple roles of interferon regulatory factor family in health and disease.Signal transduction and targeted therapy · 2024Review
- Disturbed Complement Receptor Expression Pattern of B Cells Is Enhanced by Toll-like Receptor CD180 Ligation in Diffuse Cutaneous Systemic Sclerosis.International journal of molecular sciences · 2024Article
- Context-dependent activation of STING-interferon signaling by CD11b agonists enhances anti-tumor immunity.Cancer cell · 2023Article
- Transcriptomic analysis of pathways associated with ITGAV/alpha(v) integrin-dependent autophagy in human B cells.Autophagy · 2023Article
- Altered Membrane Expression and Function of CD11b Play a Role in the Immunosuppressive Effects of Morphine on Macrophages at the Nanomolar Level.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Dysregulated low-density granulocyte contributes to early spontaneous abortion.Frontiers in immunology · 2023Article
- Soluble ITGaM and ITGb2 Integrin Subunits Are Involved in Long-Term Pulmonary Complications after COVID-19 Infection.Journal of clinical medicine · 2023Article
- Article
- Is cell regeneration and infiltration a double edged sword for porcine aortic valve deterioration? A large cohort of histopathological analysis.BMC cardiovascular disorders · 2022Article
- CD11b suppresses TLR activation of nonclassical monocytes to reduce primary graft dysfunction after lung transplantation.The Journal of clinical investigation · 2022Article
- CD11b agonists offer a novel approach for treating lupus nephritis.Translational research : the journal of laboratory and clinical medicine · 2022Review
6 more citing papers are in PubMed but not listed here.
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Authors and funding
44 authors at 15 institutions in 4 countries.
Funding
Abstract
Genetic variations in the ITGAM gene (encoding CD11b) strongly associate with risk for systemic lupus erythematosus (SLE). Here we have shown that 3 nonsynonymous ITGAM variants that produce defective CD11b associate with elevated levels of type I interferon (IFN-I) in lupus, suggesting a direct link between reduced CD11b activity and the chronically increased inflammatory status in patients. Treatment with the small-molecule CD11b agonist LA1 led to partial integrin activation, reduced IFN-I responses in WT but not CD11b-deficient mice, and protected lupus-prone MRL/Lpr mice from end-organ injury. CD11b activation reduced TLR-dependent proinflammatory signaling in leukocytes and suppressed IFN-I signaling via an AKT/FOXO3/IFN regulatory factor 3/7 pathway. TLR-stimulated macrophages from CD11B SNP carriers showed increased basal expression of IFN regulatory factor 7 (IRF7) and IFN-β, as well as increased nuclear exclusion of FOXO3, which was suppressed by LA1-dependent activation of CD11b. This suggests that pharmacologic activation of CD11b could be a potential mechanism for developing SLE therapeutics.
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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.