ArticleScientific reports2015
GPRC6A mediates Alum-induced Nlrp3 inflammasome activation but limits Th2 type antibody responses.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- The calcium-sensing receptor in sepsis and septic shock, mechanistic pathways and translational perspectives: a systematic review.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Pooled it
- Aluminum adjuvants differentially induce IL-1β release in vitro yet share NLRP3 inflammasome-independent adjuvant effects in vivo.Scientific reports · 2026Article
- Nutrient sensing receptor GPRC6A regulates mTORC1 signaling and Tau biology.Neurobiology of disease · 2025Article
- Review
- The role of cell death pathways in respiratory viral infection and vaccination: two sides of the same coin.Frontiers in immunology · 2025Review
- Vaccines and Dementia: Part I. Non-Specific Immune Boosting with BCG: History, Ligands, and Receptors.Journal of Alzheimer's disease : JAD · 2024Review
- Review
- Mining chicken ileal microbiota for immunomodulatory microorganisms.The ISME journal · 2023Article
- NLRP3 Inflammasome's Activation in Acute and Chronic Brain Diseases-An Update on Pathogenetic Mechanisms and Therapeutic Perspectives with Respect to Other Inflammasomes.Biomedicines · 2023Review
- Nano alum: A new solution to the new challenge.Human vaccines & immunotherapeutics · 2022Review
- Undercarboxylated, But Not Carboxylated, Osteocalcin Suppresses TNF-α-Induced Inflammatory Signaling Pathway in Myoblasts.Journal of the Endocrine Society · 2022Article
- Integrative biology defines novel biomarkers of resistance to strongylid infection in horses.Scientific reports · 2021Article
- Pore-forming alpha-hemolysin efficiently improves the immunogenicity and protective efficacy of protein antigens.PLoS pathogens · 2021Article
- Strategies for Vaccination: Conventional Vaccine Approaches Versus New-Generation Strategies in Combination with Adjuvants.Pharmaceutics · 2021Review
- Polymeric Nanoparticle-Based Vaccine Adjuvants and Delivery Vehicles.Current topics in microbiology and immunology · 2021Review
- Roles of bone-derived hormones in type 2 diabetes and cardiovascular pathophysiology.Molecular metabolism · 2020Review
- Review
- Better Adjuvants for Better Vaccines: Progress in Adjuvant Delivery Systems, Modifications, and Adjuvant-Antigen Codelivery.Vaccines · 2020Review
- Unraveling the enigma: elucidating the relationship between the physicochemical properties of aluminium-based adjuvants and their immunological mechanisms of action.Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology · 2018Review
- Synthetic nanovaccines for immunotherapy.Journal of controlled release : official journal of the Controlled Release Society · 2017Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alum adjuvanticity is still an unknown mechanism despite the frequent use as vaccine adjuvant in humans. Here we show that Alum-induced inflammasome activation in vitro and in vivo is mediated by the G protein-coupled receptor GPRC6A. The Alum-induced humoral response in vivo was independent of the inflammasome because Nlrp3-/- and ASC-/- mice responded normally to Alum and blockade of IL-1 had no effect on antibody production. In contrast, Alum adjuvanticity was increased in GPRC6A-/- mice resulting in increased antibody responses and increased Th2 cytokine concentrations compared to wildtype mice. In vitro activation of GPRC6A-/- splenic B cells also induced increased IgG1 concentrations compared to wildtype B cells. For the first time, we show GPRC6A expression in B cells, contributing to the direct effects of Alum on those cells. B cell produced immunostimulatory IL-10 is elevated in GPRC6A-/- B cells in vitro and in vivo. Our results demonstrate a dual role of GPRC6A in Alum adjuvanticity. GPCR6A activation by Alum leads to the initiation of innate inflammatory responses whereas it is an important signal for the limitation of adaptive immune responses induced by Alum, partially explained by B cell IL-10.
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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.