Enhanced cGAS-STING–dependent interferon signaling associated with mutations in ATAD3A
| Autor: | Stéphanie Chhun, Yanick J. Crow, Henna Tyynismaa, Bert Callewaert, Gillian I. Rice, Manju A Kurian, Christine Bodemer, Edwin Carter, Lien De Somer, Luis Seabra, Simon Holden, Hugh J. McMillan, Brigitte Bader-Meunier, Kristin Suetens, Timothy Wai, Lucy Grove, Sylvie Fraitag, Erika Della Mina, Ashish Dhir, Fran Faes, Marie Hully, Mathieu P Rodero, Pascale de Lonlay, Marie-Louise Frémond, Alice Lepelley, Daniela Buhas, David A. Dyment, Carine Wouters, Erika Van Nieuwenhove, Lise Waumans |
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| Přispěvatelé: | STEMM - Stem Cells and Metabolism Research Program, Centre of Excellence in Stem Cell Metabolism, Staff Services, Henna Tyynismaa / Principal Investigator, Neuroscience Center, Helsinki Institute of Life Science HiLIFE, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), University Hospitals Leuven [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Centre national de Référence (CNR) des Hantavirus [UZ Leuven, Belgium], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Manchester [Manchester], University of Edinburgh, McGill University Health Center [Montreal] (MUHC), McGill University = Université McGill [Montréal, Canada], Ghent University Hospital, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Children's Hospital of Eastern Ontario [Ottawa, Canada], West Suffolk Hospital Foundation Trust [Bury St Edmunds, UK] (WSHFT), Addenbrooke's Hospital, Cambridge University NHS Trust, University College of London [London] (UCL), University of Ottawa [Ottawa], University of Helsinki, Université Paris Descartes - Paris 5 (UPD5), Biologie mitochondriale – Mitochondrial biology, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Y.J. Crow acknowledges that this project has received funding from the European Research Council under the European Union’s Horizon 2020 research and innovation program (grant agreement 786142), a state subsidy managed by the National Research Agency (France) under the 'Investments for the Future' program bearing the reference ANR-10-IAHU-01, and the National Institute for Health Research UK Rare Genetic Disease Research Consortium. The project was supported by MSDAVENIR (Devo-Decode Project). E. Van Nieuwenhove acknowledges the Research Foundation Flanders (Fonds voor Wetenschappelijk Onderzoek Vlaanderen, grant 1S22716N). B. Callewaert is a Senior Clinical Investigator of the Research Foundation Flanders. Ghent University Hospital, University Hospital Leuven, and Hôpital Universitaire, ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), European Project: 786142,ERC-2017-ADG,E-T1IFNs(2018), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut Pasteur [Paris]-Université de Paris (UP)-Centre National de la Recherche Scientifique (CNRS), Lepelley, alice, Instituts Hospitalo-Universitaires - Institut Hospitalo-Universitaire Imagine - - Imagine2010 - ANR-10-IAHU-0001 - IAHU - VALID, Elaboration of the type I interferonopathies - E-T1IFNs - - ERC-2017-ADG2018-11-01 - 2023-10-31 - 786142 - VALID |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
MITOCHONDRIAL-DNA THP-1 Cells [SDV]Life Sciences [q-bio] medicine.disease_cause DNA Mitochondrial/genetics 0302 clinical medicine Interferon DUPLICATIONS Medicine and Health Sciences Immunology and Allergy Child Genes Dominant AICARDI-GOUTIERES SYNDROME 0303 health sciences Mutation Gene knockdown I INTERFERON MEMBRANE-PROTEIN CHOLESTEROL INDUCTION Scleroderma Systemic/genetics Nucleotidyltransferases 3. Good health [SDV] Life Sciences [q-bio] Stimulator of interferon genes Child Preschool Mitochondrial Proteins/genetics Female Signal transduction RNASEH2B medicine.drug RECURRENT DE-NOVO Signal Transduction Mitochondrial DNA Interferons/genetics Mitochondrial disease Immunology Biology DNA Mitochondrial ATPases Associated with Diverse Cellular Activities/genetics Mitochondrial Proteins 03 medical and health sciences Young Adult medicine Humans Membrane Proteins/genetics Gene 030304 developmental biology Scleroderma Systemic Membrane Proteins medicine.disease Molecular biology DYSFUNCTION Nucleotidyltransferases/genetics ATPases Associated with Diverse Cellular Activities Interferons 3111 Biomedicine 030217 neurology & neurosurgery |
| Zdroj: | Lepelley, A, Mina, E D, Nieuwenhove, E V, Waumans, L, Fraitag, S, Rice, G I, Dhir, A, Frémond, M-L, Rodero, M P, Seabra, L, Carter, E, Bodemer, C, Buhas, D, Callewaert, B, Lonlay, P D, Somer, L D, Dyment, D A, Faes, F, Grove, L, Holden, S, Hully, M, Kurian, M A, McMillan, H J, Suetens, K, Tyynismaa, H, Chhun, S, Wai, T, Wouters, C, Bader-Meunier, B & Crow, Y J 2021, ' Enhanced cGAS-STING–dependent interferon signaling associated with mutations in ATAD3A ', Journal of Experimental Medicine, vol. 218, no. 10, e20201560 . https://doi.org/10.1084/jem.20201560 Journal of Experimental Medicine Journal of Experimental Medicine, Rockefeller University Press, 2021, 218 (10), pp.e20201560. ⟨10.1084/jem.20201560⟩ Journal of Experimental Medicine, 2021, 218 (10), pp.e20201560. ⟨10.1084/jem.20201560⟩ Lepelley, A, Della Mina, E, Van Nieuwenhove, E, Waumans, L, Fraitag, S, Rice, G I, Dhir, A, Frémond, M-L, Rodero, M P, Seabra, L, Carter, E, Bodemer, C, Buhas, D, Callewaert, B, de Lonlay, P, De Somer, L, Dyment, D A, Faes, F, Grove, L, Holden, S, Hully, M, Kurian, M A, McMillan, H J, Suetens, K, Tyynismaa, H, Chhun, S, Wai, T, Wouters, C, Bader-Meunier, B & Crow, Y J 2021, ' Enhanced cGAS-STING-dependent interferon signaling associated with mutations in ATAD3A ', Journal of Experimental Medicine . https://doi.org/10.1084/jem.20201560 JOURNAL OF EXPERIMENTAL MEDICINE |
| ISSN: | 0022-1007 1540-9538 |
| Popis: | Mitochondrial DNA (mtDNA) has been suggested to drive immune system activation, but the induction of interferon signaling by mtDNA has not been demonstrated in a Mendelian mitochondrial disease. We initially ascertained two patients, one with a purely neurological phenotype and one with features suggestive of systemic sclerosis in a syndromic context, and found them both to demonstrate enhanced interferon-stimulated gene (ISG) expression in blood. We determined each to harbor a previously described de novo dominant-negative heterozygous mutation in ATAD3A, encoding ATPase family AAA domain-containing protein 3A (ATAD3A). We identified five further patients with mutations in ATAD3A and recorded up-regulated ISG expression and interferon α protein in four of them. Knockdown of ATAD3A in THP-1 cells resulted in increased interferon signaling, mediated by cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING). Enhanced interferon signaling was abrogated in THP-1 cells and patient fibroblasts depleted of mtDNA. Thus, mutations in the mitochondrial membrane protein ATAD3A define a novel type I interferonopathy. ispartof: JOURNAL OF EXPERIMENTAL MEDICINE vol:218 issue:10 ispartof: location:United States status: published |
| Databáze: | OpenAIRE |
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