ArticleCell research2019
Glycolipid iGb3 feedback amplifies innate immune responses via CD1d reverse signaling.
Article in Cell research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Incidence and risk factors of asymptomatic bacteriuria in patients with type 2 diabetes mellitus: a meta-analysis.Endocrine · 2023Pooled it
- CD1d remodels the tumor-infiltrating myeloid populations controlling antitumor immunity.The Journal of experimental medicine · 2026Article
- CD1d functions as a ligand for PIRA2 to drive macrophage activation in nonalcoholic fatty liver disease.Cell death & disease · 2026Article
- Monocyte-mediated mechanisms in idiopathic pulmonary fibrosis: opportunities for early intervention.Apoptosis : an international journal on programmed cell death · 2026Review
- Toll-like receptors in innate immunity and inflammation: from fundamental biology to clinic insights.Immunity & inflammation · 2026Review
- B cell-expressed CD1d promotes MPL/TDCM lipid emulsion adjuvant effects in polysaccharide vaccines.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Global trends and frontiers in iNKT cells: a bibliometric and visualized analysis.Frontiers in immunology · 2025Article
- RBM25 is required to restrain inflammation via ACLY RNA splicing-dependent metabolism rewiring.Cellular & molecular immunology · 2024Article
- CD1 molecules: Beyond antigen presentation.Molecular immunology · 2024Review
- Contribution of NKT cells and CD1d-expressing cells in obesity-associated adipose tissue inflammation.Frontiers in immunology · 2024Review
- Lipids regulate peripheral serotonin release via gut CD1d.Immunity · 2023Article
- Article
- Histone demethylase KDM5B licenses macrophage-mediated inflammatory responses by repressing Nfkbia transcription.Cell death and differentiation · 2023Article
- CD1d-dependent rewiring of lipid metabolism in macrophages regulates innate immune responses.Nature communications · 2022Article
- Admission lysophosphatidylethanolamine acyltransferase level predicts the severity and prognosis of community-acquired pneumonia.Infection · 2021Article
- CD1d1 intrinsic signaling in macrophages controls NLRP3 inflammasome expression during inflammation.Science advances · 2020Article
- Three Novel Players: PTK2B, SYK, and TNFRSF21 Were Identified to Be Involved in the Regulation of Bovine Mastitis Susceptibility via GWAS and Post-transcriptional Analysis.Frontiers in immunology · 2019Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cross-talk between cellular lipid metabolism and the innate immune responses remains obscure. In addition to presenting lipid antigens to Natural Killer T-cells (NKT cells), the Cluster of Differentiation 1D Glycoprotein (CD1d) might mediate reverse signaling in antigen-presenting cells (APCs). Here we found CD1d deficiency attenuated Toll-like receptor (TLR)-triggered inflammatory innate responses in macrophages and dendritic cells, protecting mice from endotoxin shock. TLR activation in macrophages induced metabolic changes of glycosphingolipids (GSLs), among which glycolipid isoglobotrihexosylceramide (iGb3) was rapidly produced. The endogenously generated iGb3 bound CD1d in endosomal compartments and then synergized with the initially activated TLR signal to induce Tyr332 phosphorylation of CD1d intracellular domain. This led to the recruitment and activation of proline-rich tyrosine kinase 2 (Pyk2). Pyk2 interacted with IκB kinase β (IKKβ) and TANK-binding kinase 1 (TBK1), and enhanced tyrosine phosphorylation of Tyr188/199 of IKKβ and Tyr179 of TBK1 and thus, their activation to promote full activation of TLR signaling. Thus, intracellular CD1d reverse signaling, triggered by endogenous iGb3, amplifies inflammatory innate responses in APCs. Our findings identify a non-canonical function of CD1d reverse signaling activated by lipid metabolite in the innate 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.