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Series GSE217030 Query DataSets for GSE217030
Status Public on Nov 30, 2024
Title Loss of RPA1 impairs peripheral T cell homeostasis and exacerbates inflammatory damage through triggering T cell necroptosis
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary The peripheral T cell pool is maintained at dynamic homeostasis throughout life. This is achieved through fine-tuning of thymic output and self-renewal of naïve T cells. Dysregulation of T cell homeostasis has been implicated in autoimmune diseases, yet little is known about the homeostatic mechanisms. Here, we report that the replication protein A1 (RPA1) is upregulated during T cell activation. Utilizing T cell-specific Rpa1-deficient (Rpa1fl/fl Cd4-cre) mice, we find that loss of Rpa1 restrains peripheral CD8+ T cell population and limits TCR repertoire diversity. Clinical analysis reveals that the mRNA level of RPA1 is reduced in patients with ulcerative colitis. Accordingly, Rpa1fl/fl Cd4-cre mice exhibit increased susceptibility to inflammatory diseases, including colitis and hepatitis. Mechanistically, RPA1 deficiency triggers necroptotic T cell death following TCR engagement, which in turn results in damage-associated molecular patterns (DAMPs) leakage and leukocyte recruitment, consequently exacerbating inflammatory damage. These studies thus uncover that RPA1 acts as a guardian of T cell clonal expansion that is essential for T cell homeostasis.
 
Overall design Study of colon infiltration immune cells from WT or CKO mice in the context of experimental colitis using 10x scRNA-seq technologies.
 
Contributor(s) Song J, Zhang X, Lu D
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Submission date Nov 01, 2022
Last update date Nov 30, 2024
Contact name Jia Song
E-mail(s) [email protected]
Phone +18830053918
Organization name Peking University
Street address Peking University School of Medicine, 38 Xueyuan Road, Haidian District, Beijing
City Beijing
State/province China
ZIP/Postal code 100080
Country China
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (2)
GSM6703834 Colon WT
GSM6703835 Colon CKO
Relations
BioProject PRJNA896595

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE217030_RAW.tar 62.3 Mb (http)(custom) TAR (of MTX, TSV)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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