2021 Fiscal Year Annual Research Report
The role of the transcription factor Tox2 in Treg and Tfh biology
| Project/Area Number |
18K07175
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| Research Institution | Osaka University |
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Principal Investigator |
ウィング ジェイムス 大阪大学, 感染症総合教育研究拠点, 准教授 (00648694)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Keywords | Regulatory T-cells / T-follicular regulatory / T-follicular helper / Mass Cytometry (CyTOF) |
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| Outline of Annual Research Achievements |
The aim of this study was to explore the role of the Tox2 gene in the biology of Treg and Tfr cells using a Treg specific conditional knockout of Tox2 in Foxp3+ regulatory T cells. To study the role of Tox2 in T cell biology and beyond, we used single cell mass cytometry to analyze the entire immune cell pool. We found little differences in the T cell immune composition under steady-state conditions, and only after vaccination did Tox2 seem to have an effect. In the T cell subset analyses, we found increased levels of Tfh and enhanced Tfh/Tfr ratios in Peyer’s patches in Tox2 knockout mice after NP-OVA vaccination. Furthermore, deletion of the Tox2 gene in Treg also affected the B cell composition, with increased frequency of Germinal centers and early plasmablasts. The Germinal centers additionally expressed higher levels of IgA suggesting a specific role for Tox2 expressing Tregs in the regulation of mucosal immunity. In addition to the conditional knockout system, we also overexpressed the Tox2 gene in conventional T-cells and Tregs using a viral vector and assessed the changes to gene expression by RNA-sequencing analysis. A number of significantly differentially expressed Tfh-associated genesand Tfr-associated transcription factors Ascl2 and Bach2 were upregulated in Tox2 transfected cells. These results confirm that Tox2 controls the expression of key Tfh, Tfr, and Treg genes. Taken together, our results demonstrate for the first time that Tox2 plays an important role in regulatory cells after immune challenge.
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