ArticleCell2015
Limiting Cholesterol Biosynthetic Flux Spontaneously Engages Type I IFN Signaling.
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Article in Cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 301 papers.
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301citing papers in PubMed
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301 citing papers in PubMed, 437 citations in OpenAlex.
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- Integrative proteomics and lipidomics reveals dual roles for lipid droplets in the host cell antiviral response.Nature communications · 2026Article
- Macrophage signaling and function are regulated by distinct sterol biochemistries.Journal of lipid research · 2026Article
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- Systemic multi-omics analysis reveals interferon response heterogeneity and links lipid metabolism to immune alterations in severe COVID-19.Genome medicine · 2026Article
- TGFβ primes alveolar-like macrophages to induce type I IFN following TLR2 activation.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
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- Downmodulation of cholesterol biosynthetic network governs activation of the innate immune response to Japanese encephalitis virus infection.Journal of virology · 2026Article
- Opportunities and challenges of targeting cGAS-STING in cancer.Nature reviews. Cancer · 2026Review
- Molecular mechanisms in rare proteasomopathies.EULAR rheumatology open · 2026Review
- Ceramide as a key regulatory factor in the impact of dietary inflammatory index on plaque stability.Scientific reports · 2026Article
- Beyond Viral Restriction: The Metabolic Dimensions of Interferon-Stimulated Genes in Antiviral Immunity.Viruses · 2026Review
- An updated overview of lipid-regulated immunobiology in macrophages.Acta biochimica et biophysica Sinica · 2026Review
- Environmental and genetic risk factors of depression converge on neuronal dysfunction driven by changes in cholesterol homeostasis.Developmental cell · 2026Article
- Preoperative LDL-C and mortality after cardiac valve surgery: a retrospective cohort study on the mediating role of inflammatory risk.Lipids in health and disease · 2026Article
241 more citing papers are in PubMed but not listed here.
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Authors and funding
24 authors at 6 institutions in 2 countries.
Autumn G YorkDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Kevin J WilliamsDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Joseph P ArgusDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Quan D ZhouDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Gurpreet BrarDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Laurent VergnesDepartment of Human Genetics, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA 90095, USA.
Elizabeth E GrayDepartment of Immunology, University of Washington, 750 Republican Street, Box 358059, Seattle, WA 98109, USA.
Anjie ZhenDivision of Hematology/Oncology, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA 90095, USA; UCLA AIDS Institute and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, Los Angeles, CA 90095, USA.
Nicholas C WuDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Douglas H YamadaImmuno-Oncology Discovery Research; Janssen Research & Development, LLC, Spring House, PA 19477, USA.
Cameron R CunninghamDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Elizabeth J TarlingDivision of Cardiology, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Moses Q WilksCenter for Advanced Medical Imaging Sciences, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA.
David CaseroDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA 90095, USA.
David H GrayDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Amy K YuDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Eric S WangDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
David G BrooksPrincess Margaret Cancer Center, Immune Therapy Program, University Health Network, Toronto, ON M5G 2M9, Canada; Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Ren SunDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Scott G KitchenDivision of Hematology/Oncology, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA 90095, USA; UCLA AIDS Institute and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, Los Angeles, CA 90095, USA.
Ting-Ting WuDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Karen ReueDepartment of Human Genetics, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Daniel B StetsonDepartment of Immunology, University of Washington, 750 Republican Street, Box 358059, Seattle, WA 98109, USA.
Steven J BensingerDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA 90095, USA. Electronic address: sbensinger@mednet.ucla.edu.
University of California, Los Angeles · USUniversity of Washington · USBroad Center · USJanssen (United States) · USMassachusetts General Hospital · USPrincess Margaret Cancer Centre · CA
Funding
UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0MSystems genomics of metabolic syndrome traitsP01HL028481 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI REUE, KAREN · 1985 to 2019
$50.2MVirology CoreP30AI028697 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ANTON, PETER A · 1991 to 2018
$39.9MUCLA-Caltech Medical Scientist Training ProgramT32GM008042 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI AJIJOLA, OLUJIMI A, DAWSON, DAVID WAYNE · 1985 to 2023
$29.9MThe Lipin Protein Family and Triglyceride Metabolism P01HL090553 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI YOUNG, STEPHEN G. · 2008 to 2018
$23.3MVirology CoreP01CA177322 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SUN, REN · 2014 to 2018
$8.7MIntracellular nucleic acid detection in autoimmunityR01AI084914 · NIAID · UNIVERSITY OF WASHINGTON · PI STETSON, DANIEL B · 2010 to 2024
$7.2MMechanisms of Viral PersistenceR01AI085043 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BROOKS, DAVID G · 2010 to 2023
$4.5MReactivation of Kaposi's Sarcoma-Associated HerpesvirusR01CA091791 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SUN, REN · 2001 to 2017
$4.4MInterdisciplinary Training in Virology and Gene TherapyT32AI060567 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WU, TING-TING · 2004 to 2018
$3.4MDetermining the Impact of SREBP on Adaptive ImmunityR01AI093768 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BENSINGER, STEVEN J · 2012 to 2015
$1.5MRole of ABCG1 in lipid homeostasis, inflammation and innate immunityR00HL118161 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TARLING, ELIZABETH JOANNA · 2015 to 2017
$740kNCATS NIH HHS UL1 TR000124NCATS NIH HHS UL1TR000124NCI NIH HHS P01 CA177322NCI NIH HHS R01 CA091791NCI NIH HHS R01 CA177322NCRR NIH HHS S10 RR026744NCRR NIH HHS S10RR026744NHLBI NIH HHS HL126556NHLBI NIH HHS P01 HL028481NHLBI NIH HHS P01HL028481NHLBI NIH HHS P01 HL090553NHLBI NIH HHS R00 HL118161NHLBI NIH HHS R21 HL126556NIAID NIH HHS AI093768NIAID NIH HHS P30 AI028697NIAID NIH HHS R01 AI084914NIAID NIH HHS R01 AI085043NIAID NIH HHS R01 AI093768NIAID NIH HHS R21 AI110306NIAID NIH HHS T32 AI 060567NIAID NIH HHS T32 AI060567NIDCR NIH HHS R01 DE023519NIDCR NIH HHS R21 DE023519NIGMS NIH HHS T32 GM008042NIGMS NIH HHS T32 GM008469
Abstract
Cellular lipid requirements are achieved through a combination of biosynthesis and import programs. Using isotope tracer analysis, we show that type I interferon (IFN) signaling shifts the balance of these programs by decreasing synthesis and increasing import of cholesterol and long chain fatty acids. Genetically enforcing this metabolic shift in macrophages is sufficient to render mice resistant to viral challenge, demonstrating the importance of reprogramming the balance of these two metabolic pathways in vivo. Unexpectedly, mechanistic studies reveal that limiting flux through the cholesterol biosynthetic pathway spontaneously engages a type I IFN response in a STING-dependent manner. The upregulation of type I IFNs was traced to a decrease in the pool size of synthesized cholesterol and could be inhibited by replenishing cells with free cholesterol. Taken together, these studies delineate a metabolic-inflammatory circuit that links perturbations in cholesterol biosynthesis with activation of innate immunity.
Indexed as
Immunity, InnateSignal TransductionAnimalsCell Line, TumorCholesterolHumansInterferon beta-1bInterferon-gammaMembrane ProteinsMevalonic AcidMiceMice, Inbred C57BLSterol Regulatory Element Binding Protein 1Sterol Regulatory Element Binding Protein 2CholesterolInterferon beta-1bInterferon-gammaMembrane ProteinsMevalonic AcidSrebf1 protein, mouseSrebf2 protein, mouseSterol Regulatory Element Binding Protein 1Sterol Regulatory Element Binding Protein 2
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