ArticleThe Journal of clinical investigation2014
Shifting FcγRIIA-ITAM from activation to inhibitory configuration ameliorates arthritis.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
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Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 89 citations in OpenAlex.
- Fc Gamma Receptors as Regulators of Bone Destruction in Inflammatory Arthritis.Frontiers in immunology · 2021Pooled it
- Unravelling mechanisms regulating Mincle activation.Communications biology · 2026Review
- Association between Lyn tyrosine kinase and renal injury in patients with systemic lupus erythematosus.Renal failure · 2025Article
- A genetically determined molecular switch modulates the anti-inflammatory potential of human IgA.Frontiers in immunology · 2025Article
- Immunoglobulins: Mechanistic Approaches in Moderation of Various Inflammatory and Anti-inflammatory Pathways.Current pharmaceutical biotechnology · 2025Review
- Submicron immunoglobulin particles exhibit FcγRII-dependent toxicity linked to autophagy in TNFα-stimulated endothelial cells.Cellular and molecular life sciences : CMLS · 2024Article
- The Role of LC3-Associated Phagocytosis Inhibits the Inflammatory Response in Aspergillus fumigatus Keratitis.Investigative ophthalmology & visual science · 2024Article
- hFcγRIIa: a double-edged sword in osteoclastogenesis and bone balance in transgenic mice.Frontiers in immunology · 2024Article
- The dualistic role of Lyn tyrosine kinase in immune cell signaling: implications for systemic lupus erythematosus.Frontiers in immunology · 2024Review
- AutoCore: A network-based definition of the core module of human autoimmunity and autoinflammation.Science advances · 2023Article
- Analysis of Novel Immunological Biomarkers Related to Rheumatoid Arthritis Disease Severity.International journal of molecular sciences · 2023Article
- Article
- Ablation of SYK Kinase from Expanded Primary Human NK Cells via CRISPR/Cas9 Enhances Cytotoxicity and Cytokine Production.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Antibody Fc-chimerism and effector functions: When IgG takes advantage of IgA.Frontiers in immunology · 2023Review
- Improving Antibody Therapeutics by Manipulating the Fc Domain: Immunological and Structural Considerations.Annual review of biomedical engineering · 2022Review
- Role of inhibitory signaling in peripheral B cell tolerance.Immunological reviews · 2022Review
- Spatial organization of FcγR and TLR2/1 on phagosome membranes differentially regulates their synergistic and inhibitory receptor crosstalk.Scientific reports · 2021Article
- Inhibitory affinity modulation of FcγRIIA ligand binding by glycosphingolipids by inside-out signaling.Cell reports · 2021Article
- Review
- DNGR-1 limits Flt3L-mediated antitumor immunity by restraining tumor-infiltrating type I conventional dendritic cells.Journal for immunotherapy of cancer · 2021Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Rheumatoid arthritis-associated (RA-associated) inflammation is mediated through the interaction between RA IgG immune complexes and IgG Fc receptors on immune cells. Polymorphisms within the gene encoding the human IgG Fc receptor IIA (hFcγRIIA) are associated with an increased risk of developing RA. Within the hFcγRIIA intracytoplasmic domain, there are 2 conserved tyrosine residues arranged in a noncanonical immunoreceptor tyrosine-based activation motif (ITAM). Here, we reveal that inhibitory engagement of the hFcγRIIA ITAM either with anti-hFcγRII F(ab')2 fragments or intravenous hIgG (IVIg) ameliorates RA-associated inflammation, and this effect was characteristic of previously described inhibitory ITAM (ITAMi) signaling for hFcαRI and hFcγRIIIA, but only involves a single tyrosine. In hFcγRIIA-expressing mice, arthritis induction was inhibited following hFcγRIIA engagement. Moreover, hFcγRIIA ITAMi-signaling reduced ROS and inflammatory cytokine production through inhibition of guanine nucleotide exchange factor VAV-1 and IL-1 receptor-associated kinase 1 (IRAK-1), respectively. ITAMi signaling was mediated by tyrosine 304 (Y304) within the hFcγRIIA ITAM, which was required for recruitment of tyrosine kinase SYK and tyrosine phosphatase SHP-1. Anti-hFcγRII F(ab')2 treatment of inflammatory synovial cells from RA patients inhibited ROS production through induction of ITAMi signaling. These data suggest that shifting constitutive hFcγRIIA-mediated activation to ITAMi signaling could ameliorate RA-associated inflammation.
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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.