-
Uddannelse
Find uddannelse
Studievejledning
Kvalitet
- Forskning
-
Samarbejde
Virksomheder
Kommuner og regioner
Gymnasier
Myndigheder
-
Om AU
Organisation
Kontakt
Om AU
- Organisation
- Ledelse
- Strategi
- AU i tal
- AU's historie
- Internationalt samarbejde
- Bæredygtighed
- Campus 2.0
- Diversitet og ligestilling
- Ledige stillinger
- Presse
- Kontakt
A STING antagonist modulating the interaction with STIM1 blocks ER-to-Golgi trafficking and inhibits lupus pathology
Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review
DOI
- https://doi.org/10.1016/j.ebiom.2021.103314
Forlagets udgivne version
- Thaneas Prabakaran
- Anne Troldborg
- Sarinya Kumpunya, Chulalongkorn Univ, Chulalongkorn University, Dept Geol ,
- Isara Alee, Chulalongkorn Univ, Chulalongkorn University, Dept Geol ,
- Emilija Marinković, Technische Universität Dresden ,
- Samuel J Windross
- Ramya Nandakumar ,
- Ryo Narita
- Bao-Cun Zhang
- Mikkel Carstensen
- Pichpisith Vejvisithsakul, Mahidol University ,
- Mikkel H S Marqvorsen
- Marie B Iversen
- Christian K Holm
- Lars J Østergaard
- Finn Skou Pedersen ,
- Trairak Pisitkun, Chulalongkorn University ,
- Rayk Behrendt, Technische Universität Dresden ,
- Prapaporn Pisitkun, Mahidol University ,
- Søren R Paludan
BACKGROUND: Nucleic acids are potent stimulators of type I interferon (IFN-I) and antiviral defense, but may also promote pathological inflammation. A range of diseases are characterized by elevated IFN-I, including systemic lupus erythematosus (lupus). The DNA-activated cGAS-STING pathway is a major IFN-I-inducing pathway, and activation of signaling is dependent on trafficking of STING from the ER to the Golgi.
METHODS: Here we used cell culture systems, a mouse lupus model, and material from lupus patients, to explore the mode of action of a STING antagonistic peptide, and its ability to modulate disease processes.
FINDINGS: We report that the peptide ISD017 selectively inhibits all known down-stream activities of STING, including IFN-I, inflammatory cytokines, autophagy, and apoptosis. ISD017 blocks the essential trafficking of STING from the ER to Golgi through a mechanism dependent on the STING ER retention factor STIM1. Importantly, ISD017 blocks STING activity in vivo and ameliorates disease development in a mouse model for lupus. Finally, ISD017 treatment blocks pathological cytokine responses in cells from lupus patients with elevated IFN-I levels.
INTERPRETATION: These data hold promise for beneficial use of STING-targeting therapy in lupus.
FUNDING: The Novo Nordisk Foundation, The European Research Council, The Lundbeck Foundation, European Union under the Horizon 2020 Research, Deutsche Forschungsgemeinschaft, Chulalongkorn University.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 103314 |
| Tidsskrift | EBioMedicine |
| Vol/bind | 66 |
| Antal sider | 13 |
| DOI | |
| Status | Udgivet - jun. 2021 |
Bibliografisk note
Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.
Se relationer på Aarhus Universitet Citationsformater
ID: 215297959