PT  - JOURNAL ARTICLE
AU  - Isabelle K. Vila
AU  - Hanane Chamma
AU  - Alizée Steer
AU  - Clara Taffoni
AU  - Line S. Reinert
AU  - Evgenia Turtoi
AU  - Mathilde Saccas
AU  - Johanna Marines
AU  - Lei Jin
AU  - Xavier Bonnefont
AU  - Soren R. Paludan
AU  - Dimitrios Vlachakis
AU  - Andrei Turtoi
AU  - Nadine Laguette
TI  - Control of polyunsaturated fatty acids desaturation by Sting regulates inflammatory responses
AID  - 10.1101/2020.12.22.423950
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.12.22.423950
4099  - http://biorxiv.org/content/early/2020/12/23/2020.12.22.423950.short
4100  - http://biorxiv.org/content/early/2020/12/23/2020.12.22.423950.full
AB  - Inflammatory disorders are major health issues in which immune function and metabolic homeostasis are concertedly altered. Yet, how innate and metabolic pathways are coordinated, in homeostatic conditions, is poorly understood. Here, we demonstrate that the Stimulator of interferon genes (Sting) inhibits the Fatty acid desaturase 2 (Fads2) rate limiting enzyme in polyunsaturated Fatty acid desaturation, thereby controlling both Fatty acid (FA) metabolism and innate immunity. Indeed, we show that Sting activation increased Fads2 activity, while decreasing Fads2 levels enhanced Sting activation, establishing an anti-viral state. Remarkably, the cross-regulation between Sting and Fads2 is mediated by the cyclic GMP-AMP (cGAMP) Sting agonist and PUFAs. Indeed, PUFAs inhibit Sting activation, while cGAMP binds Fads2 and promotes its degradation. Thus, our study identifies Sting as a master regulator of the interplay between FA metabolism and inflammation.One Sentence Summary Sting inhibits polyunsaturated fatty acid metabolism.Competing Interest StatementThe authors have declared no competing interest.