ArticleProceedings of the National Academy of Sciences of the United States of America2019
The uric acid crystal receptor Clec12A potentiates type I interferon responses.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 45 citations in OpenAlex.
- CLEC-1 promotes early IFN response in cDC1s and favors immune dysregulation during sepsis in mice.iScience · 2026Article
- Targeting NK cell CLEC12B enhances cancer immunotherapy.Nature immunology · 2026Article
- ASGR2 and CLEC12A as Prognostically Relevant C-Type Lectin Hubs in Glioblastoma.International journal of molecular sciences · 2026Article
- Repurposed metformin-apigenin combination therapy for metabolic dysfunction-associated steatohepatitis: from integrative multi-omics discovery toFrontiers in pharmacology · 2026Article
- CLEC12A signaling represses protective immune responses and contributes to hippocampal pathology in neurotropic picornavirus infection.Scientific reports · 2025Article
- Emulsion adjuvant-induced uric acid release modulates optimal immunogenicity by targeting dendritic cells and B cells.NPJ vaccines · 2025Article
- Pan-cancer analysis identifies CLEC12A as a potential biomarker and therapeutic target for lung adenocarcinoma.Cancer cell international · 2025Article
- Clec12a controls colitis by tempering inflammation and restricting expansion of specific commensals.Cell host & microbe · 2025Article
- The Dectin-1 and Dectin-2 clusters: C-type lectin receptors with fundamental roles in immunity.EMBO reports · 2024Review
- Innate immune sensing of cell death in disease and therapeutics.Nature cell biology · 2024Review
- Key patient demographics shape innate immune topography in noncritical hypoxic COVID-19 pneumonia.JCI insight · 2023Article
- Identification of two early blood biomarkers ACHE and CLEC12A for improved risk stratification of critically ill COVID-19 patients.Scientific reports · 2023Article
- CLEC12A Binds toInternational journal of molecular sciences · 2023Article
- The diverse roles of C-type lectin-like receptors in immunity.Frontiers in immunology · 2023Review
- Impact of disease-modifying therapy on dendritic cells and exploring their immunotherapeutic potential in multiple sclerosis.Journal of neuroinflammation · 2022Review
- Postnatal Conditional Deletion ofBiomedicines · 2022Article
- Single-cell RNA-sequencing of peripheral blood mononuclear cells reveals widespread, context-specific gene expression regulation upon pathogenic exposure.Nature communications · 2022Article
- Vector and Host C-Type Lectin Receptor (CLR)-Fc Fusion Proteins as a Cross-Species Comparative Approach to Screen for CLR-Rift Valley Fever Virus Interactions.International journal of molecular sciences · 2022Article
- Natural antibodies and CRP drive anaphylatoxin production by urate crystals.Scientific reports · 2022Article
- The Fusion ofInternational journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The detection of microbes and damaged host cells by the innate immune system is essential for host defense against infection and tissue homeostasis. However, how distinct positive and negative regulatory signals from immune receptors are integrated to tailor specific responses in complex scenarios remains largely undefined. Clec12A is a myeloid cell-expressed inhibitory C-type lectin receptor that can sense cell death under sterile conditions. Clec12A detects uric acid crystals and limits proinflammatory pathways by counteracting the cell-activating spleen tyrosine kinase (Syk). Here, we surprisingly find that Clec12A additionally amplifies type I IFN (IFN-I) responses in vivo and in vitro. Using retinoic acid-inducible gene I (RIG-I) signaling as a model, we demonstrate that monosodium urate (MSU) crystal sensing by Clec12A enhances cytosolic RNA-induced IFN-I production and the subsequent induction of IFN-I-stimulated genes. Mechanistically, Clec12A engages Src kinase to positively regulate the TBK1-IRF3 signaling module. Consistently, Clec12A-deficient mice exhibit reduced IFN-I responses upon lymphocytic choriomeningitis virus (LCMV) infection, which affects the outcomes of these animals in acute and chronic virus infection models. Thus, our results uncover a previously unrecognized connection between an MSU crystal-sensing receptor and the IFN-I response, and they illustrate how the sensing of extracellular damage-associated molecular patterns (DAMPs) can shape the immune response.
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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.