RIPK3-MLKL necroptotic signalling amplifies STING pathway and exacerbates lethal sepsis.

ABSTRACT:

Backgrounds

The stimulator of interferon genes (STING) is an important driver in various inflammatory diseases.

Methods and results

Here, we have demonstrated that inhibition of RIPK3 and MLKL dampens STING signaling, indicating that necroptosis may be involved in sustaining STING signaling. Furthermore, RIPK3 knockout in HT-29 cells significantly suppressed STING signaling. Mechanistically, RIPK3 inhibits autophagic flux during STING activation. RIPK3 knockout inhibits STING signaling by intensifying STING autophagy. In contrast, MLKL regulates the STING pathway bidirectionally. MLKL deficiency enhances STING signaling, whereas suppression of MLKL-mediated pore formation restricts STING signaling. Mechanistically, upon abrogating the pro-necroptotic activity of MLKL, MLKL b

SUBMITTER: Zhang X 

PROVIDER: S-EPMC10359592 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature