Nadine Laguette a été distinguée de la médaille de bronze du CNRS en 2021 et a été lauréate d’une ERC STARTING GRANT. Son équipe étudie les mécanismes moléculaires qui régulent l’inflammation chronique et ses conséquences physiopathologiques. Ses travaux visent à identifier la nature, la biogénèse et la régulation des acides nucléiques pathologiques. Ces travaux ont une importance cruciale pour la compréhension des réponses anti-virales, anti-tumorales et de façon plus générale pour les pathologies présentant une inflammation chronique.

Résumé de sa présentation :

Concerted alteration of immune and metabolic homeostasis underlies several inflammation-related pathologies, ranging from metabolic syndrome to infectious diseases. Here, we explored the coordination of nucleic acid-dependent inflammatory responses and metabolic homeostasis. We reveal that the Stimulator of Interferon Genes (STING) protein regulates metabolic homeostasis through inhibition of the Fatty acid desaturase 2 (FADS2), a rate-limiting enzyme in polyunsaturated fatty acids (PUFAs) desaturation. STING ablation and agonist-mediated degradation increased FADS2 activity and led to accumulation of PUFAs that drive thermogenesis. STING agonists directly activated FADS2, promoting metabolic alterations. PUFAs in-turn inhibited STING, thereby regulating antiviral responses and contributing to resolve STING-associated inflammation. Thus, we have unveiled a negative regulatory feedback loop between STING and FADS2 that fine-tunes inflammatory responses. Our results highlight the role of metabolic alterations in human pathologies associated with aberrant STING activation and STING targeting therapies. Such implications will be discussed, notably for chronic inflammatory pathologies where STING activation has been involved.