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Single-cell RNA-sequencing of PBMCs from SAVI patients reveals disease-associated monocytes with elevated integrated stress response.
de Cevins, Camille; Delage, Laure; Batignes, Maxime; Riller, Quentin; Luka, Marine; Remaury, Anne; Sorin, Boris; Fali, Tinhinane; Masson, Cécile; Hoareau, Bénédicte; Meunier, Catherine; Parisot, Mélanie; Zarhrate, Mohammed; Pérot, Brieuc P; García-Paredes, Víctor; Carbone, Francesco; Galliot, Lou; Nal, Béatrice; Pierre, Philippe; Canard, Luc; Boussard, Charlotte; Crickx, Etienne; Guillemot, Jean-Claude; Bader-Meunier, Brigitte; Bélot, Alexandre; Quartier, Pierre; Frémond, Marie-Louise; Neven, Bénédicte; Boldina, Galina; Augé, Franck; Alain, Fischer; Didier, Michel; Rieux-Laucat, Frédéric; Ménager, Mickaël M.
Afiliación
  • de Cevins C; Université de Paris Cité, Imagine Institute, Laboratory of Inflammatory Responses and Transcriptomic Networks in Diseases, Atip-Avenir Team, INSERM UMR 1163, 75015 Paris, France; Sanofi R&D Data and Data Science, Artificial Intelligence & Deep Analytics, Omics Data Science, 1 Av Pierre Bross
  • Delage L; Université de Paris Cité, Imagine Institute Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, 75015 Paris, France; Checkpoint Immunology, Immunology and Inflammation Therapeutic Area, Sanofi, 94400 Vitry-sur-Seine, France.
  • Batignes M; Université de Paris Cité, Imagine Institute, Laboratory of Inflammatory Responses and Transcriptomic Networks in Diseases, Atip-Avenir Team, INSERM UMR 1163, 75015 Paris, France.
  • Riller Q; Université de Paris Cité, Imagine Institute Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, 75015 Paris, France.
  • Luka M; Université de Paris Cité, Imagine Institute, Laboratory of Inflammatory Responses and Transcriptomic Networks in Diseases, Atip-Avenir Team, INSERM UMR 1163, 75015 Paris, France; Labtech Single-Cell@Imagine, Imagine Institute, INSERM UMR 1163, 75015 Paris, France.
  • Remaury A; Genomics and Proteomics Groups, Translational Sciences, Sanofi R&D, 1 Av Pierre Brossolette, 91385 Chilly-Mazarin, France.
  • Sorin B; Université de Paris Cité, Imagine Institute Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, 75015 Paris, France.
  • Fali T; Université de Paris Cité, Imagine Institute, Laboratory of Inflammatory Responses and Transcriptomic Networks in Diseases, Atip-Avenir Team, INSERM UMR 1163, 75015 Paris, France.
  • Masson C; Bioinformatics Platform, Structure Fédérative de Recherche Necker, INSERM UMR1163, Université de Paris, Imagine Institute, Paris, France.
  • Hoareau B; Sorbonne Université, INSERM UMS037 PASS, Plateforme de Cytométrie (CyPS), Paris, France.
  • Meunier C; Genomics and Proteomics Groups, Translational Sciences, Sanofi R&D, 1 Av Pierre Brossolette, 91385 Chilly-Mazarin, France.
  • Parisot M; Genomics Core Facility, Institut Imagine-Structure Fédérative de Recherche Necker, INSERM U1163 et INSERM US24/CNRS UAR3633, Paris Descartes Sorbonne Paris Cite University, Paris, France.
  • Zarhrate M; Genomics Core Facility, Institut Imagine-Structure Fédérative de Recherche Necker, INSERM U1163 et INSERM US24/CNRS UAR3633, Paris Descartes Sorbonne Paris Cite University, Paris, France.
  • Pérot BP; Université de Paris Cité, Imagine Institute, Laboratory of Inflammatory Responses and Transcriptomic Networks in Diseases, Atip-Avenir Team, INSERM UMR 1163, 75015 Paris, France.
  • García-Paredes V; Université de Paris Cité, Imagine Institute, Laboratory of Inflammatory Responses and Transcriptomic Networks in Diseases, Atip-Avenir Team, INSERM UMR 1163, 75015 Paris, France.
  • Carbone F; Université de Paris Cité, Imagine Institute, Laboratory of Inflammatory Responses and Transcriptomic Networks in Diseases, Atip-Avenir Team, INSERM UMR 1163, 75015 Paris, France; Labtech Single-Cell@Imagine, Imagine Institute, INSERM UMR 1163, 75015 Paris, France.
  • Galliot L; Aix Marseille Université, CNRS, INSERM, CIML, 13288 Marseille Cedex 9, France.
  • Nal B; Aix Marseille Université, CNRS, INSERM, CIML, 13288 Marseille Cedex 9, France.
  • Pierre P; Aix Marseille Université, CNRS, INSERM, CIML, 13288 Marseille Cedex 9, France; Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, 3810-193 Aveiro, Portugal; Shanghai Institute of Immunology, Department of Microbiology and Immunology, Shanghai Jiao Tong Universit
  • Canard L; Genomics and Proteomics Groups, Translational Sciences, Sanofi R&D, 1 Av Pierre Brossolette, 91385 Chilly-Mazarin, France.
  • Boussard C; Université de Paris Cité, Imagine Institute Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, 75015 Paris, France.
  • Crickx E; Université de Paris Cité, Imagine Institute Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, 75015 Paris, France; Service de Médecine Interne, Centre national de référence des cytopénies auto-immunes de l'adulte, Hôpital Henri Mondor, Fédération Hospitalo-Universitaire
  • Guillemot JC; Genomics and Proteomics Groups, Translational Sciences, Sanofi R&D, 1 Av Pierre Brossolette, 91385 Chilly-Mazarin, France.
  • Bader-Meunier B; Pediatric Immuno-hematology and Rheumatology Department, Hôpital Necker-Enfants Malades, AP-HP. Centre Université Paris Cité, 75015 Paris, France.
  • Bélot A; International Center of Infectiology Research (CIRI), University of Lyon, INSERM U1111, Claude Bernard University, Lyon 1, CNRS, UMR5308, ENS of Lyon, Lyon, France; National Reference Center for Rheumatic, Autoimmune and Systemic Diseases in Children (RAISE), Pediatric Nephrology, Rheumatology, Derm
  • Quartier P; Pediatric Immuno-hematology and Rheumatology Department, Hôpital Necker-Enfants Malades, AP-HP. Centre Université Paris Cité, 75015 Paris, France.
  • Frémond ML; Pediatric Immuno-hematology and Rheumatology Department, Hôpital Necker-Enfants Malades, AP-HP. Centre Université Paris Cité, 75015 Paris, France; Université Paris Cité, Imagine Institute, Laboratory of Neurogenetics and Neuroinflammation, INSERM UMR 1163, 75015 Paris, France.
  • Neven B; Université de Paris Cité, Imagine Institute Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, 75015 Paris, France; Pediatric Immuno-hematology and Rheumatology Department, Hôpital Necker-Enfants Malades, AP-HP. Centre Université Paris Cité, 75015 Paris, France.
  • Boldina G; Sanofi R&D Data and Data Science, Artificial Intelligence & Deep Analytics, Omics Data Science, 1 Av Pierre Brossolette, 91385 Chilly-Mazarin, France.
  • Augé F; Sanofi R&D Data and Data Science, Artificial Intelligence & Deep Analytics, Omics Data Science, 1 Av Pierre Brossolette, 91385 Chilly-Mazarin, France.
  • Alain F; Université de Paris, Imagine Institute, INSERM UMR 1163, 75015 Paris, France; Collège de France, Paris, France; Department of Paediatric Immuno-Haematology and Rheumatology, Reference Center for Rheumatic, AutoImmune and Systemic Diseases in Children (RAISE), Hôpital Necker-Enfants Malades, Assistan
  • Didier M; Genomics and Proteomics Groups, Translational Sciences, Sanofi R&D, 1 Av Pierre Brossolette, 91385 Chilly-Mazarin, France.
  • Rieux-Laucat F; Université de Paris Cité, Imagine Institute Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, 75015 Paris, France.
  • Ménager MM; Université de Paris Cité, Imagine Institute, Laboratory of Inflammatory Responses and Transcriptomic Networks in Diseases, Atip-Avenir Team, INSERM UMR 1163, 75015 Paris, France; Labtech Single-Cell@Imagine, Imagine Institute, INSERM UMR 1163, 75015 Paris, France. Electronic address: mickael.menager
Cell Rep Med ; 4(12): 101333, 2023 12 19.
Article en En | MEDLINE | ID: mdl-38118407
ABSTRACT
Gain-of-function mutations in stimulator of interferon gene 1 (STING1) result in STING-associated vasculopathy with onset in infancy (SAVI), a severe autoinflammatory disease. Although elevated type I interferon (IFN) production is thought to be the leading cause of the symptoms observed in patients, STING can induce a set of pathways, which have roles in the onset and severity of SAVI and remain to be elucidated. To this end, we performed a multi-omics comparative analysis of peripheral blood mononuclear cells (PBMCs) and plasma from SAVI patients and healthy controls, combined with a dataset of healthy PBMCs treated with IFN-ß. Our data reveal a subset of disease-associated monocyte, expressing elevated CCL3, CCL4, and IL-6, as well as a strong integrated stress response, which we suggest is the result of direct PERK activation by STING. Cell-to-cell communication inference indicates that these monocytes lead to T cell early activation, resulting in their senescence and apoptosis. Last, we propose a transcriptomic signature of STING activation, independent of type I IFN response.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Vasculares / Interferón Tipo I Límite: Humans Idioma: En Revista: Cell Rep Med Año: 2023 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Vasculares / Interferón Tipo I Límite: Humans Idioma: En Revista: Cell Rep Med Año: 2023 Tipo del documento: Article Pais de publicación: Estados Unidos