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Autophagy and Mitophagy-Related Pathways at the Crossroads of Genetic Pathways Involved in Familial Sarcoidosis and Host-Pathogen Interactions Induced by Coronaviruses.
Pacheco, Yves; Valeyre, Dominique; El Jammal, Thomas; Vallee, Maxime; Chevalier, Fabien; Lamartine, Jérôme; Sigaudo-Roussel, Dominique; Verrier, Bernard; Israel-Biet, Dominique; Freymond, Nathalie; Cottin, Vincent; Calender, Alain.
  • Pacheco Y; Laboratory of Tissue Biology and Therapeutic Engineering, CNRS UMR5305, Claude Bernard University Lyon I, IBCP, 69007 Lyon, France.
  • Valeyre D; UMR INSERM 1272, University Sorbonne Paris Nord, Hospital Paris-Saint Joseph, 75014 Paris, France.
  • El Jammal T; Laboratory of Tissue Biology and Therapeutic Engineering, CNRS UMR5305, Claude Bernard University Lyon I, IBCP, 69007 Lyon, France.
  • Vallee M; Department of Internal Medicine, Lyon University Hospital, 69007 Lyon, France.
  • Chevalier F; Department of Bioinformatics, Hospices Civils de Lyon, 69007 Lyon, France.
  • Lamartine J; Laboratory of Tissue Biology and Therapeutic Engineering, CNRS UMR5305, Claude Bernard University Lyon I, IBCP, 69007 Lyon, France.
  • Sigaudo-Roussel D; Laboratory of Tissue Biology and Therapeutic Engineering, CNRS UMR5305, Claude Bernard University Lyon I, IBCP, 69007 Lyon, France.
  • Verrier B; Laboratory of Tissue Biology and Therapeutic Engineering, CNRS UMR5305, Claude Bernard University Lyon I, IBCP, 69007 Lyon, France.
  • Israel-Biet D; Laboratory of Tissue Biology and Therapeutic Engineering, CNRS UMR5305, Claude Bernard University Lyon I, IBCP, 69007 Lyon, France.
  • Freymond N; Department of Pulmonology AP-HP, Georges Pompidou European Hospital, 75014 Paris, France.
  • Cottin V; Department of Respiratory Medicine, Hospices Civils de Lyon, Lyon South Hospital, 69007 Lyon, France.
  • Calender A; Department of Respiratory Medicine, Hospices Civils de Lyon, National Reference Centre for Rare Pulmonary Diseases, Louis Pradel Hospital, Claude-Bernard Lyon 1, 69007 Lyon, France.
Cells ; 10(8)2021 08 05.
Article in English | MEDLINE | ID: covidwho-1348605
ABSTRACT
Sarcoidosis is a multisystem disease characterized by the development and accumulation of granulomas, the hallmark of an inflammatory process induced by environmental and/or infectious and or genetic factors. This auto-inflammatory disease mainly affects the lungs, the gateway to environmental aggressions and viral infections. We have shown previously that genetic predisposition to sarcoidosis occurring in familial cases is related to a large spectrum of pathogenic variants with, however, a clustering around mTOR (mammalian Target Of Rapamycin)-related pathways and autophagy regulation. The context of the COVID-19 pandemic led us to evaluate whether such genetic defects may increase the risk of a severe course of SARS-CoV2 infection in patients with sarcoidosis. We extended a whole exome screening to 13 families predisposed to sarcoidosis and crossed the genes sharing mutations with the list of genes involved in the SARS-CoV2 host-pathogen protein-protein interactome. A similar analysis protocol was applied to a series of 100 healthy individuals. Using ENRICH.R, a comprehensive gene set enrichment web server, we identified the functional pathways represented in the set of genes carrying deleterious mutations and confirmed the overrepresentation of autophagy- and mitophagy-related functions in familial cases of sarcoidosis. The same protocol was applied to the set of genes common to sarcoidosis and the SARS-CoV2-host interactome and found a significant enrichment of genes related to mitochondrial factors involved in autophagy, mitophagy, and RIG-I-like (Retinoic Acid Inducible Gene 1) Receptor antiviral response signaling. From these results, we discuss the hypothesis according to which sarcoidosis is a model for studying genetic abnormalities associated with host response to viral infections as a consequence of defects in autophagy and mitophagy processes.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Sarcoidosis / Autophagy / COVID-19 Type of study: Diagnostic study / Experimental Studies / Prognostic study Topics: Variants Limits: Humans Language: English Year: 2021 Document Type: Article Affiliation country: Cells10081995

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Sarcoidosis / Autophagy / COVID-19 Type of study: Diagnostic study / Experimental Studies / Prognostic study Topics: Variants Limits: Humans Language: English Year: 2021 Document Type: Article Affiliation country: Cells10081995