|
| Status |
Public on Aug 30, 2018 |
| Title |
Regulation of follicular T-helper cell positioning and function by PD-1 |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Follicular T-helper (TFH) cells highly express the programmed cell death-1 (PD-1) molecule. Whereas inhibition of T cell receptor (TCR) signaling and CD28 co-stimulation is thought to be the primary mode of PD-1 functions, how PD-1 regulates TFH development and function remains unclear. Here we show that, when engaged by the ensemble of bystander B cells constitutively expressing PD-1 ligand 1 (PD-L1), PD-1 inhibits T-cell recruitment into follicles. This inhibition involves suppression of PI3K activities downstream of follicle-guidance receptor CXCR5, is independent from co-signaling with the TCR, and necessitates ICOS signaling to overcome. PD-1 further restricts CXCR3 upregulation on TFH cells, serving to concentrate these cells toward the GC territory, where PD-L1-PD-1 interactions between individual TFH and B cells optimize B-cell competition and affinity maturation. Therefore, operating in both costimulation-independent and -dependent manners, PD-1 plays an integral role in orchestrating tissue positioning and function of TFH cells.
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| |
|
| Overall design |
Differential expression analysis between WT and Pdcd1KI/KI CXCR5hi Tfh cells
|
| |
|
| Contributor(s) |
Qi H, Shi J, Hou S, Fang Q, Liu X, Liu X |
| Citation(s) |
30076099 |
| |
| Submission date |
Mar 20, 2018 |
| Last update date |
Mar 21, 2019 |
| Contact name |
Hai Qi |
| E-mail(s) |
qihai@mail.tsinghua.edu.cn
|
| Organization name |
Tsinghua University
|
| Department |
School of Medicine
|
| Lab |
Laboratory of Dynamic Immunobiology
|
| Street address |
Tsinghuayuan Street
|
| City |
Beijing |
| State/province |
Beijing |
| ZIP/Postal code |
100084 |
| Country |
China |
| |
|
| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
|
| Samples (12)
|
|
| Relations |
| BioProject |
PRJNA439209 |
| SRA |
SRP136067 |
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