ArticleThe Journal of biological chemistry2013
Complement receptor 3 influences toll-like receptor 7/8-dependent inflammation: implications for autoimmune diseases characterized by antibody reactivity to ribonucleoproteins.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00074373 (The Research Registry for Neonatal Lupus), which is not on this map. Cited by 29 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
The Research Registry for Neonatal Lupus
Who cites it
29 citing papers in PubMed.
- A case of autoimmune hemolytic anemia with acquired functional mutation of the TLR7.Immunologic research · 2026Article
- The role of the complement system in gastrointestinal-related diseases.Frontiers in immunology · 2026Review
- CD11b agonists offer a novel approach for treating lupus nephritis.Translational research : the journal of laboratory and clinical medicine · 2022Review
- Complement-Opsonized Nano-Carriers Are Bound by Dendritic Cells (DC) via Complement Receptor (CR)3, and by B Cell Subpopulations via CR-1/2, and Affect the Activation of DC and B-1 Cells.International journal of molecular sciences · 2021Article
- Review
- B Cell αv Integrins Regulate TLR-Driven Autoimmunity.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Complement Deficiencies Result in Surrogate Pathways of Complement Activation in Novel Polygenic Lupus-like Models of Kidney Injury.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Complement and human T cell metabolism: Location, location, location.Immunological reviews · 2020Review
- Linking indirect effects of cytomegalovirus in transplantation to modulation of monocyte innate immune function.Science advances · 2020Article
- CD11b Signaling Prevents Chondrocyte Mineralization and Attenuates the Severity of Osteoarthritis.Frontiers in cell and developmental biology · 2020Article
- Mice expressing the variant rs1143679 allele of ITGAM (CD11b) show impaired DC-mediated T cell proliferation.Mammalian genome : official journal of the International Mammalian Genome Society · 2019Article
- New insights into the immune functions of complement.Nature reviews. Immunology · 2019Review
- Leukadherin-1-Mediated Activation of CD11b Inhibits LPS-Induced Pro-inflammatory Response in Macrophages and Protects Mice Against Endotoxic Shock by Blocking LPS-TLR4 Interaction.Frontiers in immunology · 2019Article
- Cis interaction between sialylated FcγRIIA and the αI-domain of Mac-1 limits antibody-mediated neutrophil recruitment.Nature communications · 2018Article
- Modulation of human Th17 cell responses through complement receptor 3 (CD11 b/CD18) ligation on monocyte-derived dendritic cells.Journal of autoimmunity · 2018Article
- Mycobacterial Phenolic Glycolipids Selectively Disable TRIF-Dependent TLR4 Signaling in Macrophages.Frontiers in immunology · 2018Article
- Microglial complement receptor 3 regulates brain Aβ levels through secreted proteolytic activity.The Journal of experimental medicine · 2017Article
- A Novel Mechanism for Generating the Interferon Signature in Lupus: Opsonization of Dead Cells by Complement and IgM.Arthritis & rheumatology (Hoboken, N.J.) · 2016Article
- More than complementing Tolls: complement-Toll-like receptor synergy and crosstalk in innate immunity and inflammation.Immunological reviews · 2016Review
- The complement receptor 3 (CD11b/CD18) agonist Leukadherin-1 suppresses human innate inflammatory signalling.Clinical and experimental immunology · 2016Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Toll-like receptor (TLR) signaling is an important component in the inflammatory response generated in diseases characterized by autoantibody reactivity to proteins such as SSA/Ro in complex with endogenous nucleic acids. Complement receptor 3 (CR3), a genetic variant of which has been identified as a risk factor in systemic lupus erythematosus, has been shown to induce tolerogenic responses in dendritic cells and suppress TLR4 responses in a murine sepsis model. Accordingly, this study addressed the hypothesis that activation of CR3, influenced by genotype of CD11b, negatively regulates TLR7/8-dependent effector function. Allosteric activation of CD11b via pretreatment with the small molecule, leukadhedrin 1 (LA1), significantly attenuated TLR7/8-induced (hY3 RNA, R848) secretion of TNFα in THP-1 cells and human macrophages isolated from donors homozygous for the ancestral common ITGAM allele at rs1143679. This inhibition was accompanied by profound degradation of the adaptor protein MyD88, an effect not observed with direct inhibition of TLR ligation by an antagonist oligonucleotide. In contrast, the addition of LA1 after incubation with the TLR agonists did not result in MyD88 degradation and subsequent attenuation of TNFα secretion. In TLR7/8-stimulated macrophages isolated from donors heterozygous for the CD11b variant, pretreatment with LA1 did not down-regulate TNFα release. These novel findings support a negative cross-talk between CR3 and TLR pathways likely to be induced by antibodies reactive with ribonucleoproteins and point to the development of CR3-specific agonists as potential therapeutics for diseases such as neonatal lupus.
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