期刊
CELLULAR & MOLECULAR IMMUNOLOGY
卷 16, 期 3, 页码 236-241出版社
CHIN SOCIETY IMMUNOLOGY
DOI: 10.1038/s41423-019-0205-5
关键词
STING; Palmitoylation; Inflammation; SAVI; Interferonopathies
类别
资金
- C.C. Klestrup og Hustru Henriette Klestrup's Mindefond
- Direktor Jacob Madsen og Hustru Olga Madsen's Fond
- Den Bohmske Fond
- Lily Benthine Lunds Fond af 1.6.1978 from the Graduate School of Health at Aarhus University
- Graduate School of Health at Aarhus University
- Japan Society for the Promotion of Science (JSPS) KAKENHI [JP17K15445]
- ONO Medical Research Foundation
- Takeda Science Foundation
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- NIH [R01-GM125944, R01-DK112854]
- American Heart Association [AHA17GRN33660955]
- JSPS KAKENHI [JP16H04782, JP15H05903]
- AMED-PRIME
- Horslevsfonden
- Agnes and Poul Friis Fond
- Brdr. Hartmanns Fond
- Oda og Hans Svenningsens Fond
- Augustinus Fonden
- Hede Nielsens Fond
Gain-of-function mutations in the STING-encoding gene TMEM173 are central to the pathology of the autoinflammatory disorder STING-associated vasculopathy with onset in infancy (SAVI). Furthermore, excessive activity of the STING signaling pathway is associated with autoinflammatory diseases, including systemic lupus erythematosus and Aicardi-Goutieres syndrome (AGS). Two independent studies recently identified pharmacological inhibitors of STING. Strikingly, both types of compounds are reactive nitro-containing electrophiles that target STING palmitoylation, a posttranslational modification necessary for STING signaling. As a consequence, the activation of downstream signaling molecules and the induction of type I interferons were inhibited. The compounds were effective at ameliorating inflammation in a mouse model of AGS and in blocking the production of type I interferons in primary fibroblasts from SAVI patients. This mini-review focuses on the roles of palmitoylation in STING activation and signaling and as a pharmaceutical target for drug development.
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