Journal
NATURE COMMUNICATIONS
Volume 9, Issue -, Pages -Publisher
NATURE RESEARCH
DOI: 10.1038/s41467-018-05861-7
Keywords
-
Categories
Funding
- Horslevsfonden
- Agnes and Poul Friis Fond
- Brdr. Hartmanns fond
- Oda og Hans Svenningsens Fond
- Augustinus Fonden
- Hede Nielsens Fond
- Riisfortfonden
- Dagmar Marshalls Fond
- Magda Sofie og Aase Lutz's mindelegat Fond
- Tomrermester Jorgen Holm og hustru Elisa F. Hansens indelegat Fond
- Fabrikant Einar Willumsens mindelegat Fond
- Laege Sofus Carl Emil Friis og Hustru Olga Doris Friis Legat
- Sapere Aude II Grant from the Independent Research Foundation Denmark [6110-00600B]
- Carlsbergfonden International Research Fellowship
- Lundbeck postdoctoral fellowship
- Lundbeck PhD fellowship
- Danish Research Council
- Department of Health Sciences at Aarhus university
Ask authors/readers for more resources
The transcription factor Nrf2 is a critical regulator of inflammatory responses. If and how Nrf2 also affects cytosolic nucleic acid sensing is currently unknown. Here we identify Nrf2 as an important negative regulator of STING and suggest a link between metabolic reprogramming and antiviral cytosolic DNA sensing in human cells. Here, Nrf2 activation decreases STING expression and responsiveness to STING agonists while increasing susceptibility to infection with DNA viruses. Mechanistically, Nrf2 regulates STING expression by decreasing STING mRNA stability. Repression of STING by Nrf2 occurs in metabolically reprogrammed cells following TLR4/7 engagement, and is inducible by a cell-permeable derivative of the TCA-cycle-derived metabolite itaconate (4-octyl-itaconate, 4-OI). Additionally, engagement of this pathway by 4-OI or the Nrf2 inducer sulforaphane is sufficient to repress STING expression and type I IFN production in cells from patients with STING-dependent interferonopathies. We propose Nrf2 inducers as a future treatment option in STING-dependent inflammatory diseases.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available