Transcriptional regulation of Treg development and function

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K15201
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49070:Immunology-related
• Research Institution: Okinawa Institute of Science and Technology Graduate University
• Principal Investigator: Koizumi Shin-ichi 沖縄科学技術大学院大学, 免疫シグナルユニット, 研究員 (70636547)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 制御性Ｔ細胞 / Treg / 転写因子 / JunB / エフェクター型制御性Ｔ細胞 / 自己免疫疾患 / ChIP-seq / effector Treg

Outline of Final Research Achievements

Regulatory T (Treg) cells need to differentiate into effector Treg (eTreg) cells to maintain immune homeostasis. I elucidated that the AP-1 transcription factor JunB is expressed in eTreg cells and promotes an IRF4-dependent transcription program. Mice lacking JunB in Treg cells develop multi-organ autoimmunity, concomitant with aberrant activation of T helper cells. JunB promotes expression of Treg effector molecules, such as ICOS and CTLA4, in BATF-dependent and BATF-independent manners, and is also required for homeostasis and suppressive functions of eTreg. Mechanistically, JunB facilitates the accumulation of IRF4 at a subset of IRF4 target sites, including those located near Icos and Ctla4. Thus, JunB is a critical regulator of IRF4-dependent Treg effector programs, highlighting important functions for AP-1 in Treg-mediated immune homeostasis.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究により、エフェクターTregの転写制御機構の一端が明らかとなった。本研究成果は、Treg、特にエフェクターTregの機能制御を介した自己免疫疾患の治療法の開発へとつながることが予想される。またそれに加え、Tregの機能を部分的に抑制することによる、副作用の少ないがん免疫療法の開発へとつながる可能性もある。