The role of the transcription factor Tox2 in Treg and Tfh biology

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K07175
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49070:Immunology-related
• Research Institution: Osaka University
• Principal Investigator: Wing James 大阪大学, 感染症総合教育研究拠点, 准教授 (00648694)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: Regulatory T-cells / T-follicular helper / T-follicular regulatory / Antibodies / Germinal center / Mass cytometry (CyTOF)

Outline of Final Research Achievements

We explored the role of the Tox2 gene in the biology of regulatory T-cells (Treg) and T-follicular regulatory cells (Tfr), that are critical to control of antibodies. Using a Treg specific Tox2 knockout system we found that loss of Tox2 in Tregs caused a functional defect and an increased number of T-cells that help antibody production (Tfh) and germinal center B-cells, the type of B-cell that produces high quality antibodies. Additionally we found increased levels of IgA antibody that is important to control of immunity at the mucosal sites such as the gut. We also overexpressed the Tox2 gene in conventional T-cells and Tregs which confirmed its function to increase genes important to control antibody regulation. Taken together, our results demonstrate for the first time that Tox2 plays an important role in regulatory cells after immune challenge.

Free Research Field

Immunology

Academic Significance and Societal Importance of the Research Achievements

This study found new information regarding the control of regulatory T-cells. Since these cells are responsible for the control of vaccine responses and autoimmunity we believe that these results may allow us to control these cells and lead to the production of improved vaccines and medicines.