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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
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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.
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Overall design |
Study of colon infiltration immune cells from WT or CKO mice in the context of experimental colitis using 10x scRNA-seq technologies.
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Contributor(s) |
Song J, Zhang X, Lu D |
Citation missing |
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Submission date |
Nov 01, 2022 |
Last update date |
Nov 30, 2024 |
Contact name |
Jia Song |
E-mail(s) |
[email protected]
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Phone |
+18830053918
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Organization name |
Peking University
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Street address |
Peking University School of Medicine, 38 Xueyuan Road, Haidian District, Beijing
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City |
Beijing |
State/province |
China |
ZIP/Postal code |
100080 |
Country |
China |
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Platforms (1) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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Samples (2) |
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Relations |
BioProject |
PRJNA896595 |
Supplementary file |
Size |
Download |
File type/resource |
GSE217030_RAW.tar |
62.3 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
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