ArticleImmunity2025
Particle uptake by macrophages triggers bifurcated transcriptional pathways that differentially regulate inflammation and lysosomal gene expression.
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Article in Immunity, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18citing papers in PubMed
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18 citing papers in PubMed.
- CpG content contributes to tissue-resident macrophage enhancer selection.Nucleic acids research · 2026Article
- Article
- Risk Factors for Cardiovascular Disease: Epidemiology, Screening, Prevention, and Therapeutic Interventions.MedComm · 2026Review
- Engineered Carbon Dots from a Traditional Herb Pair Orchestrate Concurrent Antioxidant and AP-1-Mediated Inflammation to Attenuate Renal Ischemia-Reperfusion Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Is Gout an Autoinflammatory Disease?Current rheumatology reports · 2026Review
- Polystyrene microplastic-induced pathophysiology is driven by disruption of efferocytosis.Immunity · 2026Article
- Article
- Advances in post-translational and epigenetic modification of hyperuricemia-to-gout progression: mechanisms and therapeutic targets.Frontiers in cell and developmental biology · 2026Review
- Epigenetic regulation of cardiac physiology and pathophysiology: biological sex matters.The journal of cardiovascular aging · 2026Article
- Trained immunity in gout: epigenetic and metabolic reprogramming of innate immune memory.Frontiers in immunology · 2026Review
- ENT3: A lysosomal urate transporter regulating urate disposition and macrophage inflammation.iScience · 2025Article
- Targeted nanodelivery strategies for atrial fibrillation: concomitant targeting of fibrosis suppression and electrical conduction restoration through advanced nanobiotechnology.Journal of nanobiotechnology · 2025Review
- Efferocytosis in Health and Disease.MedComm · 2025Review
- Chromatin structural gene expression stratifies cardiac cell populations in health and disease.Epigenetics · 2025Article
- Gouty inflammation: genetic mechanisms towards flare therapy.Current opinion in rheumatology · 2025Review
- Follow the Molecule from Crystal Arthropathy to Comorbidities: The 2024 G-CAN Gold Medal Award Awardee Lecture.Gout, urate, and crystal deposition disease · 2025Article
- Cryptotanshinone differentially induces cell death inCancer drug resistance (Alhambra, Calif.) · 2025Article
- Qifu Huazhuo formula for gout recurrence prevention: an interim analysis combining clinical outcomes with proteomic and metabolomic profiling.Frontiers in pharmacology · 2025Article
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Authors and funding
30 authors.
Isidoro CoboDivision of Clinical Immunology & Rheumatology, Department of Medicine, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; CAMBAC (Comprehensive Arthritis, Musculoskeletal, Bone and Autoimmunity Center), University of Alabama at Birmingham, Birmingham, CA, USA. Electronic address: isidorocobo@uabmc.edu.
Jessica Murillo-SaichDivision of Rheumatology, Allergy, and Immunology, UCSD School of Medicine, 9500 Gilman Drive, La Jolla, San Diego, CA, USA.
Mohnish AlishalaDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, San Diego, CA, USA.
Stephen CalderonDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, San Diego, CA, USA.
Roxana CorasDivision of Rheumatology, Allergy, and Immunology, UCSD School of Medicine, 9500 Gilman Drive, La Jolla, San Diego, CA, USA.
Benjamin HemmingDivision of Clinical Immunology & Rheumatology, Department of Medicine, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Faith InkumDivision of Clinical Immunology & Rheumatology, Department of Medicine, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Fiorella RosasDivision of Clinical Immunology & Rheumatology, Department of Medicine, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Riku TakeiDivision of Clinical Immunology & Rheumatology, Department of Medicine, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Nathan SpannDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, San Diego, CA, USA.
Thomas A ProhaskaDepartment of Medicine, University of California, San Diego, La Jolla, San Diego, CA, USA.
Paulo V G AlabarseVA San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA 92161, USA.
Se-Jin JeongCardiovascular Division, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Christian K NicklDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, San Diego, CA, USA.
Anyan ChengDivision of Rheumatology, Allergy, and Immunology, UCSD School of Medicine, 9500 Gilman Drive, La Jolla, San Diego, CA, USA.
Benjamin LiDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, San Diego, CA, USA.
Andrea VogelCenter for Pathobiochemistry & Genetics, Medical University of Vienna, Vienna, Austria.
Thomas WeichhartCenter for Pathobiochemistry & Genetics, Medical University of Vienna, Vienna, Austria.
José J FusterCentro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain; CIBER en Enfermedades Cardiovasculares (CIBER-CV), Madrid, Spain.
Thomas LeDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, San Diego, CA, USA.
Tara R BradstreetDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
Ashlee M WebberDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
Brian T EdelsonDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
Babak RazaniVascular Medicine Institute, Department of Medicine, University of Pittsburgh School of Medicine and UPMC, Pittsburgh, PA, USA; Division of Cardiology, Pittsburgh VA Medical Center, Pittsburgh, PA, USA.
Benjamin L EbertDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Howard Hughes Medical Institute, Boston, MA, USA.
Reshma TanejaDepartment of Physiology, Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Robert TerkeltaubDivision of Rheumatology, Allergy and Immunology, Department of Medicine, University of California, 9500 Gilman Drive, La Jolla, San Diego, CA 92093, USA.
Ru Liu BryanVA San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA 92161, USA.
Monica GumaDivision of Rheumatology, Allergy, and Immunology, UCSD School of Medicine, 9500 Gilman Drive, La Jolla, San Diego, CA, USA; Department of Medicine, Autonomous University of Barcelona, Plaça Cívica, Bellaterra, Barcelona 08193, Spain.
Christopher K GlassDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, San Diego, CA, USA. Electronic address: cglass@health.ucsd.edu.
Funding
Tissue-specific roles of FXR in CVD and NASHP01HL147835 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI EVANS, RONALD M · 2020 to 2024
$12.2MTranscriptional co-regulators and macrophage gene expressionR01DK091183 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLASS, CHRISTOPHER K · 2011 to 2025
$9.9MROS Modulation of Innate and Adaptive Immunity in RAP30AR048311 · NIAMS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI MOUNTZ, JOHN D · 2001 to 2017
$9.5MEXPERIMENTAL ENDOCRINOLOGY AND METABOLISMT32DK007044 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Amit Majithia · 1986 to 2026
$4.6MRheumatic Diseases Research Training GrantT32AR064194 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GARY S FIRESTEIN, Monica Guma · 2013 to 2026
$3.8MRegulation of Immune Responses to Mycobacterium tuberculosis InfectionR01AI132653 · NIAID · WASHINGTON UNIVERSITY · PI EDELSON, BRIAN TODD, STALLINGS, CHRISTINA LEIGH · 2018 to 2022
$3.0MTargeting hexokinase-2 in rheumatoid arthritisR01AR073324 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GUMA, MONICA · 2018 to 2022
$2.4MIllumina NovaSeq 6000 Sequencing SystemS10OD026929 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JEPSEN, KRISTEN LYNN · 2019 to 2019
$600kJEOL JEM-1400Plus Transmission Electron MicroscopeS10OD023527 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FARQUHAR, MARILYN GIST · 2017 to 2017
$579kNHLBI NIH HHS P01 HL147835NIAID NIH HHS R01 AI132653NIAMS NIH HHS P30 AR048311NIAMS NIH HHS R01 AR073324NIAMS NIH HHS T32 AR064194NIDDK NIH HHS R01 DK091183NIDDK NIH HHS T32 DK007044NIH HHS S10 OD023527NIH HHS S10 OD026929
Abstract
Exposure to particles is a driver of several inflammatory diseases. Here, we investigated macrophage responses to monosodium urate crystals, calcium pyrophosphate crystals, aluminum salts, and silica nanoparticles. While each particle induced a distinct gene expression pattern, we identified a common inflammatory signature and acute activation of lysosomal acidification genes. Using monosodium urate crystals as a model, we demonstrated that this lysosomal gene program is regulated by a 5'-prime-AMP-activated protein kinase (AMPK)-dependent transcriptional network, including TFEB, TFE3, and the epigenetic regulators DNA methyl transferase 3a (DNMT3A) and DOT1L. This lysosomal acidification program operates in parallel with, but largely independently of, a JNK-AP-1-dependent network driving crystal-induced chemokine and cytokine expression. These findings reveal a bifurcation in pathways governing inflammatory and lysosomal responses, offering insights for treating particle-associated diseases.
Indexed as
InflammationLysosomesMacrophagesAMP-Activated Protein KinasesAnimalsBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsDNA Methyltransferase 3AGene Expression RegulationHumansMiceNanoparticlesSignal TransductionSilicon DioxideTranscription, GeneticUric AcidAMP-Activated Protein KinasesBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsDNA Methyltransferase 3ASilicon DioxideUric AcidAMPKepigenetic regulationJNKlysosomemacrophagesparticlestranscription
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