19:10 - 21:00
Room: Ishikawa Ongakudō Interchange Hall
Poster Session
Identification of an essential epigenetic regulator of early iNKT cell development
Maia Inoue1, Kazuo Okamoto1, Tomoki Nakashima2, Hiroshi Takayanagi1
1Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan, 2Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan

Invariant natural killer T (iNKT) cells are positively selected by the glycolipid-CD1d complex on CD4+CD8+ double positive cells, and undergo differentiation from stage 0 to stage 3 cells in the thymus. Transcription factors critical for each developmental stages have been reported including PLZF and T-bet. However, epigenetic regulators that contribute to iNKT cell development are poorly elucidated. Here we identified a histone modifying enzyme (termed Himez) as an essential regulator of iNKT cell development at the early stage. Himez epigenetically regulates the expression of various genes related to cell cycle and survival in many tissues. Since Himez is highly expressed in T cells, we newly generated Himez-floxed mice and then crossed Himez-floxed mice with Cd4-Cre mice to generate T cell-specific Himez knockout mice. These mice possessed normal thymic cellularity. The frequencies of Treg cells were mildly decreased in the thymus but not in the spleen of Himezf/Δ Cd4-Cre mice. On the other hand, iNKT cells were almost absent in the thymus, spleen and liver of Himezf/Δ Cd4-Cre mice, due to an impaired differentiation at stage 1. Mixed bone marrow chimera experiments demonstrated that Himez regulates iNKT cell development in a cell intrinsic manner. The transcriptome analysis using stage 1 iNKT cells revealed a role of Himez in the regulation of genes related to the proliferation and apoptosis of iNKT cells. Collectively, Himez plays an essential role in early iNKT cell development by regulating gene expression.


Reference:
Mo-P15-8
Session:
Poster Session 15 “Innate cells including ILC, NK, mast cell and γδT cells”
Presenter/s:
Maia Inoue
Presentation type:
Poster Presentation
Room:
Ishikawa Ongakudō Interchange Hall
Date:
Monday, 30 October 2017
Time:
19:10 - 21:00
Session times:
19:10 - 21:00