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| Status |
Public on Aug 14, 2023 |
| Title |
TOX induces T cell IL-10 production in a BATF-dependent manner |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
TOX is a member of the HMG-Box transcription factors and plays important roles in thymic T cell development. Outside of the thymus, however, TOX is also highly expressed by CD8 and CD4 T cells in various states of activation and in settings of cancer and autoimmune disease. In CD4 T cells, TOX has been primarily studied in T follicular helper (TFH) cells where it , along with TOX2 promotes TFH differentiation by regulating key TFH-associated genes and suppressing CD4 cytotoxic T cell differentiation. However, the role of TOX in other Th cell subtypes is less clear. In our study, we show that TOX is expressed in several physiologically-activated Th subtypes and its ectopic expression modestly enhances the in vitro differentiation of Th2 and Treg cells. TOX overexpression also induced the expression of a small number of genes in unpolarized Th cells involved in cell activation (Pdcd1, PD-1), cellular trafficking (Ccl3, Ccl4, Xcl1) and in suppressing inflammation (Il10) that was conserved in multiple Th subtypes. We additionally show that TOX co-occupies these genes with the transcription factor BATF and that TOX-induced expression of IL-10, but not PD-1, is BATF-dependent. Based on these data, we propose a model where TOX regulates Th cell chemotactic genes involved in facilitating dendritic cell-T cell interactions and aids in the resolution or prevention of inflammation through the production of IL-10.
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| Overall design |
We transduced naïve CD4 T cells that had been activated for 2 days with EV-RV or TOX-RV under non-polarizing (i.e. anti-CD3, anti-CD28 and IL-2 only) conditions as we initially wanted to explore non-Th lineage specific effects. After 5 days of culture, we re-stimulated the cells using anti-CD3 and anti-CD28 as previously reported, sorted the GFP+ cells and performed RNA-seq on RNAs isolated from these cells
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| Contributor(s) |
Canaria DA, Yan B, Wang M, Rodriguez A, Campbell C, Wang L, Kazemian M, Olson MR |
| Citation(s) |
38054003 |
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| Submission date |
Aug 08, 2023 |
| Last update date |
Dec 14, 2023 |
| Contact name |
D. Alejandro Canaria |
| E-mail(s) |
dcanaria@purdue.edu
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| Organization name |
Purdue University
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| Street address |
201 S University St
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| City |
West Lafayette |
| State/province |
IN |
| ZIP/Postal code |
47907 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (4)
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| GSM7696611 |
CD4 T cells from spleen transduced with empty vector replicate 1 |
| GSM7696612 |
CD4 T cells from spleen transduced with empty vector replicate 2 |
| GSM7696613 |
CD4 T cells from spleen transduced with retroviruses encoding TOX replicate 1 |
| GSM7696614 |
CD4 T cells from spleen transduced with retroviruses encoding TOX replicate 2 |
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| Relations |
| BioProject |
PRJNA1003420 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE240348_RAW.tar |
1.8 Mb |
(http)(custom) |
TAR (of RESULTS) |
| GSE240348_TPM_allsamples.csv.gz |
473.7 Kb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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