ArticleJournal of immunology (Baltimore, Md. : 1950)2012
Complement activation product C5a is a selective suppressor of TLR4-induced, but not TLR3-induced, production of IL-27(p28) from macrophages.
Article in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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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.
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Who cites it
34 citing papers in PubMed, 54 citations in OpenAlex.
- A novel long-acting C5a-blocking cyclic peptide prevents sepsis-induced organ dysfunction via effective blockade of the inflammatory cascade.Signal transduction and targeted therapy · 2025Article
- Tranexamic Acid and Systemic Complement Activation in Traumatic Brain Injury Patients.Journal of the American College of Surgeons · 2025Article
- Evaluating the usefulness of C5 and C5AR1 as genetic biomarkers of IgA-mediated vasculitis.Molecular medicine (Cambridge, Mass.) · 2025Article
- Neutrophil diversity and function in health and disease.Signal transduction and targeted therapy · 2024Review
- Externalized histones fuel pulmonary fibrosis via a platelet-macrophage circuit of TGFβ1 and IL-27.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Antiviral response and immunopathogenesis of interleukin 27 in COVID-19.Archives of virology · 2023Article
- IL-27 Enhances γδ T Cell-Mediated Innate Resistance to Primary Hookworm Infection in the Lungs.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- New Insights into the Role of the Complement System in Human Viral Diseases.Biomolecules · 2022Review
- Circulating immune-complexes of IgG/IgM bound to B2-glycoprotein-I associated with complement consumption and thrombocytopenia in antiphospholipid syndrome.Frontiers in immunology · 2022Observational
- Synergistic Effects of Toll-Like Receptor 1/2 and Toll-Like Receptor 3 Signaling Triggering Interleukin 27 Gene Expression in Chikungunya Virus-Infected Macrophages.Frontiers in cell and developmental biology · 2022Article
- Renal diseases and the role of complement: Linking complement to immune effector pathways and therapeutics.Advances in immunology · 2021Review
- Interleukin-27 and Its Diverse Effects on Bacterial Infections.Frontiers in immunology · 2021Review
- Bacterial polyphosphates interfere with the innate host defense to infection.Nature communications · 2020Article
- IL-27 regulation of innate immunity and control of microbial growth.Future science OA · 2020Review
- New insights into the immune functions of complement.Nature reviews. Immunology · 2019Review
- The pituitary gland prevents shock-associated death by controlling multiple inflammatory mediators.Biochemical and biophysical research communications · 2019Article
- Prostaglandin E2 Inhibition of IL-27 Production in Murine Dendritic Cells: A Novel Mechanism That Involves IRF1.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- More than complementing Tolls: complement-Toll-like receptor synergy and crosstalk in innate immunity and inflammation.Immunological reviews · 2016Review
- C5L2, the Second C5a Anaphylatoxin Receptor, Suppresses LPS-Induced Acute Lung Injury.American journal of respiratory cell and molecular biology · 2016Article
- Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
There is accumulating evidence that the complement activation product, C5a, can orchestrate cellular immune functions. IL-27(p28/EBI3) is an emerging key player essential for regulating inflammatory responses and T cells. In this article, we report that C5a robustly suppressed IL-27(p28) gene expression and release in peritoneal macrophages. These cells from C57BL/6J mice abundantly produced IL-27(p28) after engagement of either the TLR3 (polyinosinic-polycytidylic acid) or TLR4 (LPS) receptor. Genetic deficiency of either TLR4 or LBP completely incapacitated the ability of macrophages to secrete IL-27(p28) in response to LPS. IL-27(p28)-producing macrophages also expressed the C5aR receptor, thus displaying an IL-27(p28)(+)F4/80(+)C5aR(+) phenotype. C5a suppressed IL-27(p28) in LPS-stimulated macrophages via interactions with the C5aR receptor rather than the C5L2 receptor. After endotoxemia, C5aR(-/-) mice displayed higher plasma levels of IL-27(p28) compared with C57BL/6J mice. C5a did not affect the release of IL-27(p28) or the frequency of IL-27(p28)(+)F4/80(+) macrophages after engagement of TLR3. Mechanistically, LPS activated both the NF-κB and the PI3K/Akt pathways, whereas C5a activated only the PI3K/Akt pathway. Engagement of PI3K/Akt was inhibitory for IL-27(p28) production, because PI3K/Akt pharmacologic blockade resulted in increased amounts of IL-27(p28) and reversed the suppressive effects of C5a. Blockade of PI3K/Akt in endotoxemic C57BL/6J mice resulted in higher generation of IL-27(p28). In contrast, the PI3K/Akt pathway was not involved in TLR3-mediated release of IL-27(p28). These data provide new evidence about how complement activation may selectively interfere with production of T cell regulatory cytokines by APCs in the varying contexts of either bacterial (TLR4 pathway) or viral (TLR3 pathway) infection.
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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.