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Series GSE240348 Query DataSets for GSE240348
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
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.
 
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
 
Contributor(s) Canaria DA, Yan B, Wang M, Rodriguez A, Campbell C, Wang L, Kazemian M, Olson MR
Citation(s) 38054003
Submission date Aug 08, 2023
Last update date Dec 14, 2023
Contact name D. Alejandro Canaria
E-mail(s) dcanaria@purdue.edu
Organization name Purdue University
Street address 201 S University St
City West Lafayette
State/province IN
ZIP/Postal code 47907
Country USA
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (4)
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
Relations
BioProject PRJNA1003420

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

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 SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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