Analysis and Synthesis of Multidimensional Immune Organ Network

2016 Fiscal Year Final Research Report

• Project Area: Analysis and synthesis of multi-dimensional immune organ network
• Project/Area Number: 24111001
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The University of Tokushima
• Principal Investigator: TAKAHAMA Yousuke 徳島大学, 先端酵素学研究所, 教授 (20183858)
• Co-Investigator(Kenkyū-buntansha): 渡邊 武 公益財団法人田附興風会, 医学研究所, 特任研究指導者 (40028684) ; 湊 長博 京都大学, 医学(系)研究科(研究院), 教授 (40137716) ; 宮坂 昌之 大阪大学, その他部局等, 名誉教授 (50064613) ; 高田 慎治 大学共同利用機関法人自然科学研究機構(岡崎共通研究施設), 基礎生物学研究所, 教授 (60206753) ; 福井 宣規 九州大学, 生体防御医学研究所, 教授 (60243961) ; 長澤 丘司 大阪大学, 生命機能研究科, 教授 (80281690) ; 高木 淳一 大阪大学, たんぱく質研究所, 教授 (90212000)
• Project Period (FY): 2012-06-28 – 2017-03-31
• Keywords: 免疫学 / ストローマ細胞 / 免疫の場 / リンパ器官 / 免疫空間

Outline of Final Research Achievements

The findings include that (1) Foxc1 is a critical regulator of haematopoietic stem cell niche formation, (2) medullary thymic epithelial stem cells maintain a functional thymus to ensure lifelong central T cell tolerance, (3) TCR affinity for thymoproteasome-dependent positively selecting peptides conditions antigen responsiveness in CD8+ T cells, and (4) fibroblastic reticular cell-derived lysophosphatidic acid regulates T-cell motility within the lymph nodes. It was also found that (5) the transcription factor EPAS1 links DOCK8 deficiency to atopic skin inflammation via IL-31 induction, (6) lysosomal sorting of amyloid-beta by the SORLA receptor is impaired by a familial Alzheimer’s disease mutation, (7) a CD153+CD4+ T follicular cell population with cell-senescence features plays a crucial role in lupus pathogenesis via osteopontin production, and (8) gel-trapped lymphorganogenic chemokines trigger artificial tertiary lymphoid organs and mount adaptive immune responses in vivo.

Free Research Field

免疫学