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Notch signaling protects CD4 T cells from STING-mediated apoptosis during acute systemic inflammation
- Source :
- Science Advances
- Publication Year :
- 2020
-
Abstract
- Notch or STING, which is in charge of CD4 T cell fate?<br />Dysregulation of T cell apoptosis contributes to the pathogenesis of acute systemic inflammation–induced immunosuppression, as seen in sepsis and trauma. However, the regulatory mechanisms of T cell apoptosis are unclear. Activation of stimulator of interferon genes (STING) has been shown to induce T cell apoptosis. Notch was previously identified as the top negative regulator of STING in macrophages through a kinase inhibitor library screening. However, how Notch signaling regulates STING activation in T cells is unknown. Here, using a γ-secretase inhibitor to block Notch signaling, we found that Notch protected CD4 T cells from STING-mediated apoptosis during endotoxemia. Mechanistically, Notch intracellular domain (NICD) interacted with STING at the cyclic dinucleotide (CDN) binding domain and competed with CDN to inhibit STING activation. In conclusion, our data reveal a previously unidentified role of Notch in negative regulation of STING-mediated apoptosis in CD4 T cells.
- Subjects :
- CD4-Positive T-Lymphocytes
medicine.medical_treatment
Immunology
Notch signaling pathway
Apoptosis
Systemic inflammation
Pathogenesis
03 medical and health sciences
0302 clinical medicine
medicine
Humans
Health and Medicine
Research Articles
030304 developmental biology
Inflammation
0303 health sciences
Multidisciplinary
Chemistry
SciAdv r-articles
Immunosuppression
eye diseases
Sting
030220 oncology & carcinogenesis
Stimulator of interferon genes
Cancer research
medicine.symptom
Amyloid Precursor Protein Secretases
Binding domain
Signal Transduction
Research Article
Subjects
Details
- ISSN :
- 23752548
- Volume :
- 6
- Issue :
- 39
- Database :
- OpenAIRE
- Journal :
- Science advances
- Accession number :
- edsair.doi.dedup.....73577faf4efce9432836174d687b4884