RT Journal Article
SR Electronic
T1 Notch signaling protects CD4 T cells from STING-mediated apoptosis during acute systemic inflammation
JF Science Advances
JO Sci Adv
FD American Association for the Advancement of Science
SP eabc5447
DO 10.1126/sciadv.abc5447
VO 6
IS 39
A1 Long, Junke
A1 Yang, Chenxuan
A1 Zheng, Yawen
A1 Loughran, Patricia
A1 Guang, Fu
A1 Li, Yiming
A1 Liao, Hong
A1 Scott, Melanie J.
A1 Tang, Daolin
A1 Billiar, Timothy R.
A1 Deng, Meihong
YR 2020
UL http://advances.sciencemag.org/content/6/39/eabc5447.abstract
AB 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.