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| Status |
Public on Feb 19, 2024 |
| Title |
PD-1 restrains thymic IL-2 production and regulatory T cell development |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Inhibitory proteins, such as programmed cell death protein 1 (PD-1), have been extensively studied in peripheral T cell responses to foreign, self, and neoantigens. Notably, these proteins are first expressed during T cell development in the thymus. Reports suggest that PD-1 limits regulatory T cell (Treg) development, but the mechanism by which PD-1 exerts this function remains unknown. The present study expands the evaluation of PD-1 and its ligands in the thymus, demonstrating that some of the highest expressers of PD-1 and PD-L1 are agonist selected cells. Surprisingly, we reveal a selective role for PD-1 in regulating the developmental niche only for Tregs as other agonist selected cell populations, such as natural killer T cells, remain unchanged. We also ruled out PD-1 as a regulator of proliferation or cell death of agonist selected Tregs and further demonstrated that PD-1 deficient Tregs have reduced TCR signaling. Unexpectedly, the data suggests that PD-1 deficient thymocytes produce elevated levels of IL-2, a Treg niche limiting cytokine. Collectively, these data suggest a novel role for PD-1 in regulating IL-2 production and the concurrent agonist selection of thymic Tregs. This observation has implications for the use of checkpoint blockade in the context of cancer and infection.
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| Overall design |
Thymus from 3-week-old WT or PD-1 knockout animals (C57BL/6J) were processed for flourescence-activated cell sorting (FACS) to sort CD4+ HSA+ CD73- CD25- (CD4 single positive thymocytes) and CD4+ HSA+ CD73- CD25+ (regulatory T cells and CD25+ regulatory T cell progenitors). We sought to examine differences between the WT and PD-1 knockout cells using scRNAseq.
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| Contributor(s) |
Caruso B, Weeder BR, Thompson RF, Moran AE |
| Citation(s) |
38551395 |
| |
| Submission date |
Feb 13, 2024 |
| Last update date |
Apr 17, 2024 |
| Contact name |
Amy E Moran |
| Organization name |
Oregon Health & Science University
|
| Department |
Department of Cell, Developmental & Cancer Biology
|
| Lab |
Moran
|
| Street address |
3181 SW Sam Jackson Park Rd, Mail code KR-CDCB
|
| City |
Portland |
| State/province |
Oregon |
| ZIP/Postal code |
97239 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA1076235 |
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