Article: Chloride Homeostasis Regulates cGAS-STING Signaling.
bioRxiv : the preprint server for biology
2024
Abstract: The cGAS-STING signaling pathway has emerged as a key mediator of inflammation. However, the roles of chloride homeostasis on this pathway are unclear. Here, we uncovered a correlation between chloride homeostasis and cGAS-STING signaling. We found that ... ...
| Abstract | The cGAS-STING signaling pathway has emerged as a key mediator of inflammation. However, the roles of chloride homeostasis on this pathway are unclear. Here, we uncovered a correlation between chloride homeostasis and cGAS-STING signaling. We found that dysregulation of chloride homeostasis attenuates cGAS-STING signaling in a lysosome-independent manner. Treating immune cells with chloride channel inhibitors attenuated 2'3'-cGAMP production by cGAS and also suppressed STING polymerization, leading to reduced cytokine production. We also demonstrate that non-selective chloride channel blockers can suppress the NPC1 deficiency-induced, hyper-activated STING signaling in skin fibroblasts derived from Niemann Pick disease type C (NPC) patients. Our findings reveal that chloride homeostasis majorly affects cGAS-STING pathway and suggest a provocative strategy to dampen STING-mediated inflammation via targeting chloride channels. |
|---|---|
| Language | English |
| Publishing date | 2024-04-09 |
| Publishing country | United States |
| Document type | Preprint |
| DOI | 10.1101/2024.04.08.588475 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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