ArticleJournal of immunology (Baltimore, Md. : 1950)2019
CD31 Acts as a Checkpoint Molecule and Is Modulated by FcγR-Mediated Signaling in Monocytes.
Article in Journal of immunology (Baltimore, Md. : 1950), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 21 citations in OpenAlex.
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- The dualistic role of Lyn tyrosine kinase in immune cell signaling: implications for systemic lupus erythematosus.Frontiers in immunology · 2024Review
- NOD2 activation enhances macrophage Fcγ receptor function and may increase the efficacy of antibody therapy.Frontiers in immunology · 2024Article
- Inhibition of BET Proteins Regulates Fcγ Receptor Function and Reduces Inflammation in Rheumatoid Arthritis.International journal of molecular sciences · 2023Article
- Vascular Cast to Program Antistenotic Hemodynamics and Remodeling of Vein Graft.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- High-Frequency Nanosecond Bleomycin Electrochemotherapy and its Effects on Changes in the Immune System and Survival.Cancers · 2022Article
- Camouflage strategies for therapeutic exosomes evasion from phagocytosis.Journal of advanced research · 2021Review
- Prognostic Implication of the Expression Level of PECAM-1 in Non-small Cell Lung Cancer.Frontiers in oncology · 2021Article
- Role of IL-4 in bone marrow driven dysregulated angiogenesis and age-related macular degeneration.eLife · 2020Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Monocytes and macrophages express FcγR that engage IgG immune complexes such as Ab-opsonized pathogens or cancer cells to destroy them by various mechanisms, including phagocytosis. FcγR-mediated phagocytosis is regulated by the concerted actions of activating FcγR and inhibitory receptors, such as FcγRIIb and SIRPα. In this study, we report that another ITIM-containing receptor, PECAM1/CD31, regulates FcγR function and is itself regulated by FcγR activation. First, quantitative RT-PCR and flow cytometry analyses revealed that human monocyte FcγR activation leads to a significant downregulation of CD31 expression, both at the message level and at surface expression, mainly mediated through FcγRIIa. Interestingly, the kinetics of downregulation between the two varied, with surface expression reducing earlier than the message. Experiments to analyze the mechanism behind this discrepancy revealed that the loss of surface expression was because of internalization, which depended predominantly on the PI3 kinase pathway and was independent of FcγR internalization. Finally, functional analyses showed that the downregulation of CD31 expression in monocytes by small interfering RNA enhanced FcγR-mediated phagocytic ability but have little effect on cytokine production. Together, these results suggest that CD31 acts as a checkpoint receptor that could be targeted to enhance FcγR functions in Ab-mediated therapies.
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Registered trials
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