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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Feb 14, 2024 |
| Title |
p16-dependent upregulation of PD-L1 impairs immunosurveillance of senescent cells [RNA-seq: Lung Alveolar Macrophages] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The accumulation of senescent cells promotes aging, but a molecular mechanism that senescent cells use to evade immune clearance and accumulate remains to be elucidated. Here, we report that p16-positive senescent cells upregulate the immune checkpoint protein programmed death-ligand 1 (PD-L1) to accumulate in aging and chronic inflammation. p16-mediated inhibition of CDK4/6 promotes PD-L1 stability in senescent cells via the downregulation of ubiquitin-dependent degradation. p16 expression in infiltrating macrophages induces an immunosuppressive environment that can contribute to an increased burden of senescent cells. Treatment with immunostimulatory anti-PD-L1 antibody enhances the cytotoxic T cell activity and leads to the elimination of p16, PD-L1-positive cells. Our study uncovers a molecular mechanism of p16-dependent regulation of PD-L1 protein stability in senescent cells and reveals the potential of PD-L1 as a target for treating senescence-mediated age-associated diseases.
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| Overall design |
Comparative gene expression profiling analysis of RNA-seq data for mouse lung alveolar macrophages (positive or negative for p16) chronically exposed to LPS (chronic inflammation) or PBS (control).
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| Contributor(s) |
Majewska J, Agrawal A, Mayo A, Roitman L, Chatterjee R, Kralova J, Landsberger T, Katzenelenbogen Y, Meir-Salame T, Hagai E, Stanojevic N, Amit I, Alon U, Krizhanovsky V |
| Citation(s) |
39103548 |
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| Submission date |
Feb 14, 2023 |
| Last update date |
Sep 12, 2024 |
| Contact name |
Valery Krizhanovsky |
| E-mail(s) |
valery.krizhanovsky@weizmann.ac.il
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| Organization name |
Weizmann Institute of Science
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| Department |
Molecular Cell Biology
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| Street address |
234 Herzl St.
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| City |
Rehovot |
| State/province |
Israel |
| ZIP/Postal code |
7610001 |
| Country |
Israel |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (16)
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| GSM7043253 |
Lung, PBS, p16 neg, 10 weeks, biol rep 1 |
| GSM7043254 |
Lung, PBS, p16 pos, 10 weeks, biol rep 1 |
| GSM7043255 |
Lung, LPS, p16 neg, 10 weeks, biol rep 1 |
| GSM7043256 |
Lung, LPS, p16 pos, 10 weeks, biol rep 1 |
| GSM7043257 |
Lung, PBS, p16 neg, 10 weeks, biol rep 2 |
| GSM7043258 |
Lung, PBS, p16 pos, 10 weeks, biol rep 2 |
| GSM7043259 |
Lung, LPS, p16 neg, 10 weeks, biol rep 2 |
| GSM7043260 |
Lung, LPS, p16 pos, 10 weeks, biol rep 2 |
| GSM7043261 |
Lung, PBS, p16 neg, 10 weeks, biol rep 3 |
| GSM7043262 |
Lung, PBS, p16 pos, 10 weeks, biol rep 3 |
| GSM7043263 |
Lung, LPS, p16 neg, 10 weeks, biol rep 3 |
| GSM7043264 |
Lung, LPS, p16 pos, 10 weeks, biol rep 3 |
| GSM7043265 |
Lung, PBS, p16 neg, 10 weeks, biol rep 4 |
| GSM7043266 |
Lung, PBS, p16 pos, 10 weeks, biol rep 4 |
| GSM7043267 |
Lung, LPS, p16 neg, 10 weeks, biol rep 4 |
| GSM7043268 |
Lung, LPS, p16 pos, 10 weeks, biol rep 4 |
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| This SubSeries is part of SuperSeries: |
| GSE225287 |
p16-dependent upregulation of PD-L1 impairs immunosurveillance of senescent cells |
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| Relations |
| BioProject |
PRJNA934896 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE225285_DESeq2_Alveolar_Macrophages.xlsx |
5.3 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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