PXD057241-1

PXD057241 is an original dataset announced via ProteomeXchange.

Title	Small intestinal γδ T17 cells promote SAE through STING/C1q-induced microglial synaptic pruning
Description	Sepsis is a severe global health issue with high mortality rates, and sepsis-associated encephalopathy (SAE) further exacerbates this risk. While recent studies have shown the migration of gut immune cells to the lungs after sepsis, their impact on the central nervous system remains unclear. Our research demonstrates that sepsis could induce the migration of IL-7Rhigh CD8low γδ T17 cells from the small intestine to the meninges, where they secrete IL-17A, impairing mitochondrial function in microglia and activating the cGAS-STING-C1q pathway. This process is accompanied by inhibited ubiquitination of STING at the K150 site, resulting in STING accumulation and increased release of C1q-tagged hippocampal synapses, which are subsequently pruned by activated microglia. Importantly, 4-Octyl itaconate mitigates the excessive synaptic pruning by inhibiting γδ T17 cell migration and promoting STING ubiquitination, thereby alleviating SAE. Our findings reveal a novel mechanism of synaptic pruning by microglia via the cGAS-STING-C1q pathway, emphasize the critical role of gut-derived γδ T17 cell migration to the meninges in SAE, and highlight the importance of STING ubiquitination in modulating C1q-mediated excessive synaptic pruning.
HostingRepository	iProX
AnnounceDate	2024-10-28
AnnouncementXML	Submission_2024-10-27_23:40:57.920.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yuming Wu
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-27 23:40:41	ID requested
⏵ 1	2024-10-27 23:40:58	announced

Dataset with its publication pending

submitter keyword: Sepsis-associated encephalopathy, "gut-brain" axis

Jiancheng Zhang
contact affiliation	Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
contact email	zhjcheng1@126.com
lab head
Yuming Wu
contact affiliation	Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
contact email	18615711896@163.com
dataset submitter

iProX dataset URI