Notch signaling protects CD4 T cells from STING-mediated apoptosis during acute systemic inflammation

Junke Long, Chenxuan Yang, Yawen Zheng, Patricia Loughran, Fu Guang, Yiming Li, Hong Liao, Melanie J. Scott, Daolin Tang, Timothy R. Billiar*, Meihong Deng*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


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.

Original languageEnglish
Article numbereabc5447
JournalScience Advances
Issue number39
StatePublished - Sep 2020
Externally publishedYes


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