SENTINEL
Financiado
Charting Cell Type-Specific Nucleic Acid Immunity
Metabolic and immune pathways form an intricate network that maintains homeostasis. We recently unveiled that the Stimulator of Interferon Genes (STING), central to triggering cytosolic dsDNA-dependent type I Interferon (IFN) resp...
Metabolic and immune pathways form an intricate network that maintains homeostasis. We recently unveiled that the Stimulator of Interferon Genes (STING), central to triggering cytosolic dsDNA-dependent type I Interferon (IFN) responses, inhibits the desaturation of essential dietary polyunsaturated fatty acids (PUFAs). STING thereby controls the generation of long-chain PUFAs (LC-PUFAs) that in turn inhibit STING activation. This double negative regulatory feedback loop operates as a key rheostat of homeostasis.
Interestingly, we found that metabolic tissues, such adipose tissues, express low levels of STING, and that in vitro adipocyte differentiation leads to STING downregulation, although they retain their ability to produce type I IFNs in respond to nucleic acid challenge. This suggests that alleviating the STING-dependent inhibition of PUFA metabolism may result from, or be required for, adipocyte differentiation or functionality. Further, this also suggests that adipocytes may possess specific STING-independent cytosolic nucleic acid detection pathways. Thus, nucleic acid detection pathways and PUFA metabolism should be interrogated concertedly, at the cellular levels, within metabolic tissues, to uncover how they define tissue-specific immune responses and regulate tissue homeostasis, in particular in pathologies presenting with chronic STING activation.
Within SENTINEL, we will combine state-of-the art biochemistry and molecular biology approaches, and cutting-edge omics tools, in vitro and in vivo to identify nucleic acid detection machineries and question the role of STING downregulation in metabolic cells. Finally, we will explore the impact of STING-dependent metabolic alterations in pathologies presenting with chronic STING activation. SENTINEL will thus chart an unexplored area of nucleic acid immunity (metabolic cell immunity), and reveal its impact on homeostasis and pathologies.
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Duración del proyecto: 65 meses
Fecha Inicio: 2023-04-07
Fecha Fin: 2028-09-30
Fecha Fin: 2028-09-30
Línea de financiación: concedida
El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2023-04-07
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-2022-COG:
ERC CONSOLIDATOR GRANTS
Cerrada
hace 2 años
Presupuesto
El presupuesto total del proyecto asciende a
2M€
Líder del proyecto
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE...
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5