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Article Dans Une Revue Cell Metabolism Année : 2022

STING orchestrates the crosstalk between polyunsaturated fatty acid metabolism and inflammatory responses

Lei Jin
  • Fonction : Auteur
Xavier Bonnefont
Olivier Schwartz

Résumé

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 STING (stimulator of interferon genes) protein regulates metabolic homeostasis through inhibition of the fatty acid desaturase 2 (FADS2) rate-limiting enzyme in polyunsaturated fatty acid (PUFA) desaturation. STING ablation and agonist-mediated degradation increased FADS2-associated desaturase activity and led to accumulation of PUFA derivatives that drive thermogenesis. STING agonists directly activated FADS2-dependent desaturation, promoting metabolic alterations. PUFAs in turn inhibited STING, thereby regulating antiviral responses and contributing to resolving 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.
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Origine : Publication financée par une institution

Dates et versions

hal-03520564 , version 1 (21-01-2022)

Licence

Paternité - Pas d'utilisation commerciale - Pas de modification

Identifiants

Citer

Isabelle Vila, Hanane Chamma, Alizée Steer, Mathilde Saccas, Clara Taffoni, et al.. STING orchestrates the crosstalk between polyunsaturated fatty acid metabolism and inflammatory responses. Cell Metabolism, 2022, 34 (1), pp.125-139.e8. ⟨10.1016/j.cmet.2021.12.007⟩. ⟨hal-03520564⟩
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