|
| Status |
Public on Jul 27, 2022 |
| Title |
Transcription factor RUNX3 mediates plasticity of ThGM cells toward Th1 phenotype. |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
GM-CSF-producing T helper (Th) cells play a crucial role in the pathogenesis of autoimmune diseases such as multiple sclerosis (MS). Recent studies have identified a distinct population of GM-CSF-producing Th cells, named ThGM cells, that also express cytokines TNF, IL-2, and IL-3, but lack expression of master transcription factors (TF) and signature cytokines of commonly recognized Th cell lineages. ThGM cells are highly encephalitogenic in a mouse model of MS, experimental autoimmune encephalomyelitis (EAE). Similar to Th17 cells, in response to IL-12, ThGM cells upregulate expression of T-bet and IFN-g and switch their phenotype to Th1. Here we show that in addition to T-bet, TF RUNX3 also contributes to the Th1 switch of ThGM cells. T-bet-deficient ThGM cells in the CNS of mice with EAE had low expression of RUNX3, and knockdown of RUNX3 expression in ThGM cells abrogated the Th1-inducing effect of IL-12. Comparison of ThGM and Th1 cell transcriptomes showed that ThGM cells expressed a set of TFs known to inhibit the development of other Th lineages. Lack of expression of lineage-specific cytokines and TFs by ThGM cells, together with expression of TFs that inhibit the development of other Th lineages, suggests that ThGM cells are a non-polarized subset of Th cells with lineage characteristics.
|
| |
|
| Overall design |
Human RNA-sequencing: Human ThGM, Th1, and GM-CSF+Th1 cells were isolated from peripheral blood of healthy donors using a combination of fllow cytometry cell sorting and cytokine sceretion assay. RNA from human ThGM, Th1, and GM-CSF+Th1 cells were isolated and their transcriptome were analyzed by RNA sequencing. MouseRNA sequencing: Mouse naive CD4+ T cells were polarized to ThGM and Th1 cells and RNA from several time points were isolated and analyzed using RNA sequencing.
|
| |
|
| Contributor(s) |
Rasouli J, Kumar G, Ertel A, Fortina P, Rostami A, Ciric B |
| Citation(s) |
35860266 |
| |
| Submission date |
Jun 09, 2022 |
| Last update date |
Jul 27, 2022 |
| Contact name |
Sankar Addya |
| E-mail(s) |
sankar.addya@jefferson.edu
|
| Organization name |
Thomas Jefferson University Hospital
|
| Department |
Kimmel Cancer Center
|
| Lab |
Cancer Genomics Lab
|
| Street address |
233 South 10th Street
|
| City |
Philadelphia |
| State/province |
PA |
| ZIP/Postal code |
19107 |
| Country |
USA |
| |
|
| Platforms (2) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (38)
|
| GSM6225731 |
GM-CSF+Th1 cells from PBMCs of donor 1 replicate 1 |
| GSM6225732 |
GM-CSF+Th1 cells from PBMCs of donor 1 replicate 2 |
| GSM6225733 |
GM-CSF+Th1 cells from PBMCs of donor 2 replicate 1 |
|
| Relations |
| BioProject |
PRJNA847542 |
Less...
More...