Research Project
Grant-in-Aid for Scientific Research (B)
免疫細胞の分裂増殖は抗原特異的なクローンを増幅するだけでなく分化方向の決定とも連動することが知られており、免疫応答の特性を決定する重要要素である。免疫応答では抗原に反応したリンパ球が適切に細胞分裂を開始し適切なタイミングで停止されなければならないが、その制御メカニズムについては十分に解明されていない。本研究課題では癌遺伝子やウイルス抗原によって活性化したB細胞の不死化前後で発現が顕著に制御される因子として新規に見出した細胞老化や癌関連遺伝子群を足掛かりとしてリンパ腫発症の新たなメカニズムに迫るとともに、リンパ球分化を細胞分裂と連動して制御する分子基盤と免疫応答特性における役割の解明を目指す。
The cell proliferation of immune cells is linked to the determination of their developmental direction and the characteristics of immune responses. We discovered the Eed gene, which constitutes the polycomb repressive complex PRC2, as an important regulator. We generated mice in which the Eed gene is deleted in T cells or B cells. We found that the thymic differentiation of iNKT cells is completely blocked and identified its specific molecular mechanisms. In germinal center B cell-specific Eed-deficient mice, we discovered that germinal center B cells, which are important for antibody affinity maturation, arrest at the early stage of differentiation, and the mechanism behind this was revealed.
本申請課題では免疫系の正常と病理に直結するリンパ球分裂増殖と分化誘導の制御機構に関し、相互に関連する細胞増殖、細胞死、不死化の分岐点となる分子実態の解明を目指し研究を行った。本研究成果をさらに発展させることで、将来的にがん治療、自己免疫疾患治療、新興感染症に対するワクチン開発など様々な医療分野で役立つ可能性がある。
All 2024 2023 2022 2021
All Journal Article (14 results) (of which Int'l Joint Research: 4 results, Peer Reviewed: 14 results, Open Access: 14 results) Presentation (41 results) (of which Int'l Joint Research: 16 results, Invited: 4 results) Book (1 results) Patent(Industrial Property Rights) (1 results)
Science Immunology
Volume: 9 Issue: 92
10.1126/sciimmunol.adi0042
Proceedings of the National Academy of Sciences
Volume: 120 Issue: 10
10.1073/pnas.2219439120
Experimental Gerontology
Volume: 174 Pages: 112130-112130
10.1016/j.exger.2023.112130
International Immunology
Volume: 35 Issue: 4 Pages: 197-207
10.1093/intimm/dxac055
Communications Biology
Volume: 6 Issue: 1 Pages: 1-14
10.1038/s42003-023-04782-6
Cancers
Volume: 15 Issue: 11 Pages: 2889-2889
10.3390/cancers15112889
Genes to Cells
Volume: - Issue: 6 Pages: 411-421
10.1111/gtc.13022
Volume: 14 Issue: 17 Pages: 4118-4118
10.3390/cancers14174118
Cells
Volume: 11 Issue: 11 Pages: 1754-1754
10.3390/cells11111754
Nat. Commun.
Volume: 13(1) Issue: 1 Pages: 1071-1071
10.1038/s41467-022-28677-y
J. Pharmacol. Sci.
Volume: 148 Issue: 3 Pages: 307-314
10.1016/j.jphs.2022.01.005
PLOS Genetics
Volume: 17 Issue: 8 Pages: 1009686-1009686
10.1371/journal.pgen.1009686
Sci. Rep.
Volume: 11 Issue: 1 Pages: 5524-5524
10.1038/s41598-021-84786-6
Life Science Alliance
Volume: 4 Issue: 4 Pages: e202000873-e202000873
10.26508/lsa.202000873