Mechanisms of regulatory T cell-mediated immune regulation

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H04747
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: The University of Tokyo (2016-2017); Institute of Physical and Chemical Research (2015)
• Principal Investigator: Hori Shohei 東京大学, 大学院薬学系研究科(薬学部), 教授 (50392113)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 免疫寛容 / 自己免疫疾患 / 制御性T細胞 / 遺伝子発現制御 / Foxp3 / BATF

Outline of Final Research Achievements

Foxp3+ regulatory T cells (Treg) are essential for the regulation of deleterious immune responses. Recent studies have shown that Treg cells change their gene expression in order to adapt to inflammatory or tissue environments to regulate immune responses. However, the molecular basis of this ability -adaptability- remains elusive. By generating mouse models harboring Foxp3 mutations identified in patients with the autoimmune disease IPEX, we have found that one mutation, A384T, induces tissue inflammation by specifically impairing the ability of Treg cells to accumulate in certain non-lymphoid tissues. Mechanistically, repressed expression of the transcription factor BATF contributed to the impaired adaptability of tissue Treg cells in the mutant mice. At the molecular level, the A384T mutation acted as a gain-of-function mutation in that it broadened the DNA-binding specificity of Foxp3. Our findings identify BATF as a critical regulator of Treg cell adaptability.

Free Research Field

免疫学