TY  - JOUR
A1  - Hansen, Anne-Louise Smidt
A1  - Buchan, Gregory J.
A1  - Rühl, Michael
A1  - Mukai, Kojiro
A1  - Salvatore, Sonia R.
A1  - Ogawa, Emari
A1  - Andersen, Sidsel
A1  - Iversen, Marie B.
A1  - Thielke, Anne L.
A1  - Gunderstofte, Camilla
A1  - Motwani, Mona
A1  - Møller, Charlotte T.
A1  - Jakobsen, Andreas S.
A1  - Fitzgerald, Katherine A.
A1  - Roos, Jessica
A1  - Lin, Rongtuan
A1  - Maier, Thorsten Jürgen
A1  - Goldbach-Mansky, Raphaela
A1  - Miner, Cathrine A.
A1  - Qian, Wei
A1  - Miner, Jonathan
A1  - Rigby, Rachel
A1  - Rehwinkel, Jan
A1  - Jakobsen, Martin R.
A1  - Arai, Hiroyuki
A1  - Taguchi, Tomohiko
A1  - Schopfer, Francisco J.
A1  - Olagnier, David
A1  - Holm, Christian K.
T1  - Nitro-fatty acids are formed in response to virus infection and are potent inhibitors of STING palmitoylation and signaling
T2  - Proceedings of the National Academy of Sciences of the United States of America
N2  - The adaptor molecule stimulator of IFN genes (STING) is central to production of type I IFNs in response to infection with DNA viruses and to presence of host DNA in the cytosol. Excessive release of type I IFNs through STING-dependent mechanisms has emerged as a central driver of several interferonopathies, including systemic lupus erythematosus (SLE), Aicardi–Goutières syndrome (AGS), and stimulator of IFN genes-associated vasculopathy with onset in infancy (SAVI). The involvement of STING in these diseases points to an unmet need for the development of agents that inhibit STING signaling. Here, we report that endogenously formed nitro-fatty acids can covalently modify STING by nitro-alkylation. These nitro-alkylations inhibit STING palmitoylation, STING signaling, and subsequently, the release of type I IFN in both human and murine cells. Furthermore, treatment with nitro-fatty acids was sufficient to inhibit production of type I IFN in fibroblasts derived from SAVI patients with a gain-of-function mutation in STING. In conclusion, we have identified nitro-fatty acids as endogenously formed inhibitors of STING signaling and propose for these lipids to be considered in the treatment of STING-dependent inflammatory diseases.
KW  - nitro-fatty acids
KW  - STING
KW  - palmitoylation
KW  - IFN
KW  - SAVI
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/48353
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-483539
SN  - 1091-6490
SN  - 0027-8424
N1  - This open access article is distributed under Creative Commons Attribution-NonCommercialNoDerivatives License 4.0 (CC BY-NC-ND)
VL  - 115
IS  - 33
SP  - E7768
EP  - E7775
PB  - National Acad. of Sciences
CY  - Washington, DC
ER  -