ArticleThe Journal of experimental medicine2021
LACC1 deficiency links juvenile arthritis with autophagy and metabolism in macrophages.
Open access · greenAbstract read
In one paragraph
Article in The Journal of experimental medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
3.2field-weighted citation impact, top 7% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 42 citations in OpenAlex.
- Type I Interferon Signature is Associated With Lung Disease, Drug-Associated Immune Reactions, and Genetic Variation in Interferon-Linked Pathways in Still Disease.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- LACC1 attenuates LPS-induced acute lung injury by inhibiting inflammatory response in alveolar macrophage through LPAR3/PI3K/AKT/mTOR signaling pathway.Biomarker research · 2026Article
- Review
- Metabolic masqueraders of paediatric and adult rheumatic diseases.Nature reviews. Rheumatology · 2026Review
- Response to Letter to the Editor.Human genomics · 2026Article
- Systems approach identifies monocyte imbalance in symptomatic and asymptomatic P. vivax malaria.Molecular systems biology · 2025Article
- Serum LACC1 level is a predictor of response to upadacitinib treatment in patients with rheumatoid arthritis: a prospective observational cohort study.European journal of medical research · 2025Observational
- Human inborn errors of immunity: 2024 update on the classification from the International Union of Immunological Societies Expert Committee.Journal of human immunity · 2025Article
- Lacc1-engineered extracellular vesicles reprogram mitochondrial metabolism to alleviate inflammation and cartilage degeneration in TMJ osteoarthritis.Journal of nanobiotechnology · 2025Article
- UFMylation of NLRP3 Prevents Its Autophagic Degradation and Facilitates Inflammasome Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Crohn's Disease-associated variant in laccase domain containing 1 (LACC1) modulates T cell gene expression, metabolism and T cell function.Nature communications · 2025Article
- Isocyanic acid-mediated NLRP3 carbamoylation reduces NLRP3-NEK7 interaction and limits inflammasome activation.Science advances · 2025Article
- How (Ultra-)Rare Gene Variants Improve Our Understanding of More Common Autoimmune and Inflammatory Diseases.ACR open rheumatology · 2025Review
- The research progress of LACC1.Frontiers in immunology · 2025Review
- Macrophages in osteoporotic fractures: from immunometabolic mechanisms to precision therapeutic approaches.Frontiers in endocrinology · 2025Review
- New discoveries in the genetics and genomics of systemic juvenile idiopathic arthritis.Expert review of clinical immunology · 2024Review
- [Monogenic variants in Laccase domain-containing 1 (LACC1) as the cause of juvenile arthritis].Zeitschrift fur Rheumatologie · 2024Review
- Precision medicine in monogenic inflammatory bowel disease: proposed mIBD REPORT standards.Nature reviews. Gastroenterology & hepatology · 2023Review
- JAK Inhibition in Juvenile Idiopathic Arthritis (JIA): Better Understanding of a Promising Therapy for Refractory Cases.Journal of clinical medicine · 2023Review
- Clinical characteristics and genotype analysis of a Chinese patient with juvenile arthritis due to novel LACC1 frameshift mutation and literature review.Molecular genetics & genomic medicine · 2023Review
Corrections and comments
- Commented on by
Authors and funding
29 authors at 10 institutions in 5 countries.
Ommar OmarjeeCentre International de Recherche en Infectiologie/International Center for Infectiology Research, Institut National de la Santé et de la Recherche Médicale, U1111, Ecole Normale Supérieure de Lyon, Université Lyon 1, Centre National de la Recherche Scientifique, UMR5308, Lyon, France.
Anne-Laure MathieuCentre International de Recherche en Infectiologie/International Center for Infectiology Research, Institut National de la Santé et de la Recherche Médicale, U1111, Ecole Normale Supérieure de Lyon, Université Lyon 1, Centre National de la Recherche Scientifique, UMR5308, Lyon, France.
Gaëlle QuiniouCentre International de Recherche en Infectiologie/International Center for Infectiology Research, Institut National de la Santé et de la Recherche Médicale, U1111, Ecole Normale Supérieure de Lyon, Université Lyon 1, Centre National de la Recherche Scientifique, UMR5308, Lyon, France.
Marion MoreewsCentre International de Recherche en Infectiologie/International Center for Infectiology Research, Institut National de la Santé et de la Recherche Médicale, U1111, Ecole Normale Supérieure de Lyon, Université Lyon 1, Centre National de la Recherche Scientifique, UMR5308, Lyon, France.
Michelle AinouzeCentre International de Recherche en Infectiologie/International Center for Infectiology Research, Institut National de la Santé et de la Recherche Médicale, U1111, Ecole Normale Supérieure de Lyon, Université Lyon 1, Centre National de la Recherche Scientifique, UMR5308, Lyon, France.
Cécile FrachetteNational Referee Centre for Rheumatic and Autoimmune Diseases in Children, RAISE, Paris and Lyon, France.
Isabelle MelkiNational Referee Centre for Rheumatic and Autoimmune Diseases in Children, RAISE, Paris and Lyon, France.
Cécile DumaineGeneral Pediatrics, Infectious Disease and Internal Medicine Department, Hôpital Robert Debre, Assistance Publique-Hôpitaux de Paris, Paris, France.
Mathieu Gerfaud-ValentinInternal Medicine, Croix Rousse Hospital, Hospices Civils de Lyon, Lyon, France.
Agnès DuquesneNational Referee Centre for Rheumatic and Autoimmune Diseases in Children, RAISE, Paris and Lyon, France.
Tilmann KallinichPediatric Pneumology, Immunology and Intensive Care Medicine, Charité University Medicine Berlin, German Rheumatism Research Center, Leibniz Association, Berlin Institute of Health, Berlin, Germany.
Eda Tahir TuranliDepartment of Molecular Biology and Genetics, Faculty of Science and Letters, Istanbul Technical University, Istanbul, Turkey.
Christophe MalcusNational Referee Centre for Rheumatic and Autoimmune Diseases in Children, RAISE, Paris and Lyon, France.
Sébastien VielNational Referee Centre for Rheumatic and Autoimmune Diseases in Children, RAISE, Paris and Lyon, France.
Rémi PescarmonaNational Referee Centre for Rheumatic and Autoimmune Diseases in Children, RAISE, Paris and Lyon, France.
Sophie Georgin-LavialleAssistance Publique-Hôpitaux de Paris, Hôpital Tenon, Sorbonne Université, Service de Médecine Interne, Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses d'Origine Inflammatoire, Paris, France.
Yvan JamillouxCentre International de Recherche en Infectiologie/International Center for Infectiology Research, Institut National de la Santé et de la Recherche Médicale, U1111, Ecole Normale Supérieure de Lyon, Université Lyon 1, Centre National de la Recherche Scientifique, UMR5308, Lyon, France.
Jean-Paul LarbreNational Referee Centre for Rheumatic and Autoimmune Diseases in Children, RAISE, Paris and Lyon, France.
Guillaume SarrabayCentre Hospitalier Universitaire Montpellier, University of Montpellier, Laboratory of Rare and Autoinflammatory Genetic Diseases and Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses d'Origine Inflammatoire, Montpellier, France.
Flora MagnottiCentre International de Recherche en Infectiologie/International Center for Infectiology Research, Institut National de la Santé et de la Recherche Médicale, U1111, Ecole Normale Supérieure de Lyon, Université Lyon 1, Centre National de la Recherche Scientifique, UMR5308, Lyon, France.
Gillian I RiceDivision of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Francoise BleicherInstitut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon 1, Centre National de la Recherche Scientifique, Ecole Normale Supérieure de Lyon, Lyon, France.
Jonathan RebouletInstitut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon 1, Centre National de la Recherche Scientifique, Ecole Normale Supérieure de Lyon, Lyon, France.
Samir MerabetInstitut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon 1, Centre National de la Recherche Scientifique, Ecole Normale Supérieure de Lyon, Lyon, France.
Thomas HenryCentre International de Recherche en Infectiologie/International Center for Infectiology Research, Institut National de la Santé et de la Recherche Médicale, U1111, Ecole Normale Supérieure de Lyon, Université Lyon 1, Centre National de la Recherche Scientifique, UMR5308, Lyon, France.
Yanick J CrowLaboratory of Neurogenetics and Neuroinflammation, Paris Descartes-Sorbonne Paris Cité University, Institut Imagine, Hôpital Necker, Paris, France.
Mathias FaureCentre International de Recherche en Infectiologie/International Center for Infectiology Research, Institut National de la Santé et de la Recherche Médicale, U1111, Ecole Normale Supérieure de Lyon, Université Lyon 1, Centre National de la Recherche Scientifique, UMR5308, Lyon, France.
Thierry WalzerCentre International de Recherche en Infectiologie/International Center for Infectiology Research, Institut National de la Santé et de la Recherche Médicale, U1111, Ecole Normale Supérieure de Lyon, Université Lyon 1, Centre National de la Recherche Scientifique, UMR5308, Lyon, France.
Alexandre BelotCentre International de Recherche en Infectiologie/International Center for Infectiology Research, Institut National de la Santé et de la Recherche Médicale, U1111, Ecole Normale Supérieure de Lyon, Université Lyon 1, Centre National de la Recherche Scientifique, UMR5308, Lyon, France.
Université Claude Bernard Lyon 1 · FRHospices Civils de Lyon · FRDélégation Paris 5 · FRHôpital Femme Mère Enfant · FRAssistance Publique – Hôpitaux de Paris · FRInserm · FRLeibniz Association · DENational Institutes of Health · USUniversité de Montpellier · FRUniversity of Manchester · GB
Funding
No grant is acknowledged in the PubMed record.
Abstract
Juvenile idiopathic arthritis is the most common chronic rheumatic disease in children, and its etiology remains poorly understood. Here, we explored four families with early-onset arthritis carrying homozygous loss-of-expression mutations in LACC1. To understand the link between LACC1 and inflammation, we performed a functional study of LACC1 in human immune cells. We showed that LACC1 was primarily expressed in macrophages upon mTOR signaling. We found that LACC1 deficiency had no obvious impact on inflammasome activation, type I interferon response, or NF-κB regulation. Using bimolecular fluorescence complementation and biochemical assays, we showed that autophagy-inducing proteins, RACK1 and AMPK, interacted with LACC1. Autophagy blockade in macrophages was associated with LACC1 cleavage and degradation. Moreover, LACC1 deficiency reduced autophagy flux in primary macrophages. This was associated with a defect in the accumulation of lipid droplets and mitochondrial respiration, suggesting that LACC1-dependent autophagy fuels macrophage bioenergetics metabolism. Altogether, LACC1 deficiency defines a novel form of genetically inherited juvenile arthritis associated with impaired autophagy in macrophages.
Indexed as
AutophagyAdenylate KinaseAdolescentAmino Acid SequenceApoptosisArthritis, JuvenileAutophagy-Related ProteinsBacteriaCell DifferentiationChildExomeFemaleHomozygoteHumansInflammasomesInflammationAdenylate KinaseAutophagy-Related ProteinsInflammasomesInterferonsIntracellular Signaling Peptides and ProteinsLACC1 protein, humanMacrophage Colony-Stimulating FactorNF-kappa BReceptors for Activated C KinaseTOR Serine-Threonine Kinases
Identifiers
What OpenQuestion holds
Textmetadata
LicenceCC BY-NC-SA
Read underepoch 390
Registered trials
None linked
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.