ADA2 is a lysosomal deoxyadenosine deaminase acting on DNA involved in regulating TLR9-mediated immune sensing of DNA.

Autor:	Greiner-Tollersrud OK; Institute of Medical Biology, University of Tromsø, Tromsø, Norway., Krausz M; Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Freiburg im Breisgau, Germany., Boehler V; Novartis Institutes for Biomedical Research, 4056 Basel, Switzerland., Polyzou A; Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany; IRCAN Institute for Research on Cancer and Aging, INSERM Unité 1081, CNRS UMR 7284, Université Côte d'Azur, Nice, France., Seidl M; Institute of Pathology, University Hospital of Düsseldorf, Düsseldorf, Germany., Spahiu A; Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Freiburg im Breisgau, Germany., Abdullah Z; Institute of Experimental Immunology, Universitätsklinikum Bonn, Bonn, Germany., Andryka-Cegielski K; Institute of Experimental Hematology and Transfusion Medicine Bonn, Bonn, Germany., Dominick FI; Institute of Experimental Hematology and Transfusion Medicine Bonn, Bonn, Germany., Huebscher K; Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Freiburg im Breisgau, Germany; Institut für Forstentomologie und Waldschutz, Albert-Ludwigs-University of Freiburg, Freiburg im Breisgau, Germany., Goschin A; Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Freiburg im Breisgau, Germany., Smulski CR; Medical Physics Department, Centro Atómico Bariloche, Comisión Nacional de Energía Atómica (CNEA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), San Carlos de Bariloche, Río Negro, Argentina., Trompouki E; Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany; IRCAN Institute for Research on Cancer and Aging, INSERM Unité 1081, CNRS UMR 7284, Université Côte d'Azur, Nice, France., Link R; Novartis Institutes for Biomedical Research, 4056 Basel, Switzerland., Ebersbach H; Novartis Institutes for Biomedical Research, 4056 Basel, Switzerland., Srinivas H; Novartis Institutes for Biomedical Research, 4056 Basel, Switzerland., Marchant M; Novartis Institutes for Biomedical Research, 4056 Basel, Switzerland., Sogkas G; Department of Rheumatology and Clinical Immunology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany; RESIST - Cluster of Excellence 2155, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany., Staab D; Novartis Institutes for Biomedical Research, 4056 Basel, Switzerland., Vågbø C; Proteomics and Modomics Experimental Core (PROMEC), Norwegian University of Science and Technology and the Central Norway Regional Health Authority, Trondheim, Norway., Guerini D; Novartis Institutes for Biomedical Research, 4056 Basel, Switzerland., Baasch S; Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Freiburg im Breisgau, Germany; Institute for Infection Prevention and Control, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Freiburg Institute for Advanced Studies (FRIAS), University of Freiburg, Freiburg, Germany., Latz E; Institute of Innate Immunity, Universitätsklinikum Bonn, Bonn, Germany., Hartmann G; Institute of Experimental Hematology and Transfusion Medicine Bonn, Bonn, Germany., Henneke P; Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Freiburg im Breisgau, Germany; Institute for Infection Prevention and Control, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Geiger R; Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland; Institute of Oncology Research, Università della Svizzera italiana, Bellinzona, Switzerland., Peng XP; Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Grimbacher B; Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Freiburg im Breisgau, Germany; RESIST - Cluster of Excellence 2155 to Hanover Medical School, Satellite Center Freiburg, Freiburg, Germany., Bartok E; Institute of Experimental Hematology and Transfusion Medicine Bonn, Bonn, Germany., Alseth I; Department of Microbiology, Oslo University Hospital, Oslo, Norway., Warncke M; Novartis Institutes for Biomedical Research, 4056 Basel, Switzerland., Proietti M; Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Freiburg im Breisgau, Germany; Department of Rheumatology and Clinical Immunology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany; RESIST - Cluster of Excellence 2155, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. Electronic address: michele.proietti@uniklinik-freiburg.de.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2024 Oct 22; Vol. 43 (11), pp. 114899. Date of Electronic Publication: 2024 Oct 22.
DOI:	10.1016/j.celrep.2024.114899
Abstrakt:	Although adenosine deaminase 2 (ADA2) is considered an extracellular ADA, evidence questions the physiological relevance of this activity. Our study reveals that ADA2 localizes within the lysosomes, where it is targeted through modifications of its glycan structures. We show that ADA2 interacts with DNA molecules, altering their sequences by converting deoxyadenosine (dA) to deoxyinosine (dI). We characterize its DNA substrate preferences and provide data suggesting that DNA, rather than free adenosine, is its natural substrate. Finally, we demonstrate that dA-to-dI editing of DNA molecules and ADA2 regulate lysosomal immune sensing of nucleic acids (NAs) by modulating Toll-like receptor 9 (TLR9) activation. Our results describe a mechanism involved in the complex interplay between NA metabolism and immune response, possibly impacting ADA2 deficiency (DADA2) and other diseases involving this pathway, including autoimmune diseases, cancer, or infectious diseases. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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