Analysis of epigenetic regulatory mechanisms of Th17 differentiation

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K19164
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Okinawa Institute of Science and Technology Graduate University
• Principal Investigator: Ishikawa Hiroki 沖縄科学技術大学院大学, 免疫シグナルユニット, 准教授 (30648621)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: Th17細胞 / 分化 / 病原性

Outline of Final Research Achievements

IL-17-producing Th17 cells comprise heterogeneous subsets exhibiting distinct pathogenicity. Although pathogenic and non-pathogenic Th17 subsets share a common Th17 transcriptional program composed of BATF, IRF4, STAT3, and RORgt, transcriptional regulatory mechanisms specific to each of these distinct Th17 subsets remain largely unknown. Here we show that an AP-1 transcription factor, JunB, is essential for induction of RORgt by facilitating DNA-binding of BATF, IRF4 and STAT3 at the Rorc locus in IL-23-dependent pathogenic Th17 cells, but not in TGF-b1-dependent non-pathogenic Th17 cells. Indeed, JUNB deficient T cells lose their ability to induce Th17-mediated experimental autoimmune encephalomyelitis (EAE) and colitis, but gut-resident Th17 cells are probably generated in a JUNB-independent manner. The selective requirement of JUNB for pathogenic Th17 differentiation suggests that the JUNB-dependent pathway may be a specific therapeutic target for autoimmune diseases.

Free Research Field

免疫学