Molecular mechanisms for CD4 T cell differentiation, aiming at generation of functional Treg cells

2016 Fiscal Year Final Research Report

• Project/Area Number: 26713019
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Immunology
• Research Institution: National Center for Global Health and Medicine (2016); Keio University (2014-2015)
• Principal Investigator: Sekiya Takashi 国立研究開発法人国立国際医療研究センター, その他部局等, 室長 (80519207)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: CD4T細胞 / 免疫寛容 / 制御性T細胞 / エピジェネティクス

Outline of Final Research Achievements

By classifying Treg precursor cells according to their developmental stages, we revealed Treg cell developmental programs which are dependent on Nr4a factors, as well as programs that are independent of Nr4a factors. In the analysis, we further elucidated that Nr4a factors act at relatively later stages in Treg cell development. Foxp3, that were induced by Nr4a factors then found to induce Nr4a factors, thus forming a positive feedback loop, sustaining Treg cell development.Furthermore, Nr4a-deficient Treg precursor cells not only complete their development to Treg cells, but they survive with an attenuated expression of apoptotic factors including Bim, thus converting to helper-T like cells with elevated expression of inflammatory cytokines that are usually not to be expressed by Treg cells but by helper T cells.

Free Research Field

免疫学