ArticleFrontiers in immunology2021
The Inhibitory Receptor CLEC12A Regulates PI3K-Akt Signaling to Inhibit Neutrophil Activation and Cytokine Release.
Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
- Hyperuricemia and Hypoxic Pulmonary Hypertension: Pathogenic Links, Clinical Evidence, and Emerging Therapeutic Insights.Cardiovascular drugs and therapy · 2026Review
- A skin-kidney neutrophil axis links ultraviolet exposure to renal angiogenesis and tissue remodeling in healthy and lupus kidneys.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Beyond pathogen recognition: C-type lectin receptors in microbiota regulation.Mucosal immunology · 2026Review
- Article
- Transcriptomic and proteomic profiling of piroplasmosis resistance in Yunnan humped cattle.BMC genomics · 2026Article
- CLL-1: An emerging target for immunotherapy in acute myeloid leukemia.Annals of hematology · 2026Review
- Article
- CLEC12A signaling represses protective immune responses and contributes to hippocampal pathology in neurotropic picornavirus infection.Scientific reports · 2025Article
- Stage-specific transcriptomic alterations in the spinal cord reveal key regulatory genes and potential therapeutic targets in a rat model of neuropathic pain.Journal of translational medicine · 2025Article
- Mechanical force-induced oncostatin M secretion by Jun-positive neutrophils promotes craniofacial bone regeneration for midface hypoplasia treatment.Stem cell research & therapy · 2025Article
- Identification of autoantibodies targeting citrullinated CLEC12A in rheumatoid arthritis patients.Journal of translational autoimmunity · 2025Article
- Signaling Pathways Involved in Acute Pancreatitis.Journal of inflammation research · 2025Review
- Epigenetic programming reshapes innate immune memory: decoding the molecular imprint of gouty inflammation.Frontiers in pharmacology · 2025Review
- Clec12a inhibits MSU-induced immune activation through lipid raft expulsion.Life science alliance · 2023Article
- Key patient demographics shape innate immune topography in noncritical hypoxic COVID-19 pneumonia.JCI insight · 2023Article
- ELMO1 Deficiency Reduces Neutrophil Chemotaxis in Murine Peritonitis.International journal of molecular sciences · 2023Article
- Behçet syndrome: The disturbed balance between anti- (CLEC12A, CLC) and proinflammatory (IFI27) gene expressions.Immunity, inflammation and disease · 2023Article
- Single cell RNA sequencing reveals distinct clusters of Irf8-expressing pulmonary conventional dendritic cells.Frontiers in immunology · 2023Article
- Neutrophil functional heterogeneity is a fixed phenotype and is associated with distinct gene expression profiles.Journal of leukocyte biology · 2022Article
- Recent progress and perspectives on the relationship between hyperuricemia and periodontitis.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
The myeloid inhibitory C-type lectin receptor CLEC12A limits neutrophil activation, pro-inflammatory pathways and disease in mouse models of inflammatory arthritis by a molecular mechanism that remains poorly understood. We addressed how CLEC12A-mediated inhibitory signaling counteracts activating signaling by cross-linking CLEC12A in human neutrophils. CLEC12A cross-linking induced its translocation to flotillin-rich membrane domains where its ITIM was phosphorylated in a Src-dependent manner. Phosphoproteomic analysis identified candidate signaling molecules regulated by CLEC12A that include MAPKs, phosphoinositol kinases and members of the JAK-STAT pathway. Stimulating neutrophils with uric acid crystals, the etiological agent of gout, drove the hyperphosphorylation of p38 and Akt. Ultimately, one of the pathways through which CLEC12A regulates uric acid crystal-stimulated release of IL-8 by neutrophils is through a p38/PI3K-Akt signaling pathway. In summary this work defines early molecular events that underpin CLEC12A signaling in human neutrophils to modulate cytokine synthesis. Targeting this pathway could be useful therapeutically to dampen inflammation.
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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.