2022 Fiscal Year Final Research Report
Experimental trials to promote mucosal barrier via enhancing function of ILC3s
Project/Area Number |
21K19486
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Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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Allocation Type | Multi-year Fund |
Review Section |
Medium-sized Section 53:Organ-based internal medicine and related fields
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Research Institution | Kyushu University |
Principal Investigator |
Sawa Shinichiro 九州大学, 生体防御医学研究所, 教授 (80611756)
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Project Period (FY) |
2021-07-09 – 2023-03-31
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Keywords | ILC3 / 細胞株 / STAT5 / レトロウイルスベクター |
Outline of Final Research Achievements |
Group3 Innate Lymphoid Cell=ILC3 is a member of innate lymphoid cells which play critical roles on the maintenance of intestinal epithelial barrier. In this project, I planed to establish novel therapeutic strategy to promotes epithelial barrier by transferring ILC3s as well as by using small chemical compounds which enhance function of ILC3s. To achieve these aims, establishment of cell lines of ILC3 is the most challenging issue which should be overcome. In this project, I tried to establish retroviral vector-based gene delivery system into ILC3s. In the first step, I succeeded in generating pMXs-tdTomato-P2A-STAT5CA plasmid, which should prolong survival of viral infected lymphocytes. In the second step, I confirmed tdTomato-P2A-STAT5CA expression in viral particle packaging cells named Phoenix cells. However, due to technical issues, in vitro culture of ILC3s from adult mice have not been succeeded.
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Free Research Field |
免疫学
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Academic Significance and Societal Importance of the Research Achievements |
ILC3は腸管バリア機能の維持に極めて重要な役割を果たすことから、「生体内における ILC3数の増加や機能増強は細菌性腸炎、ウイルス性腸炎などの感染性腸炎からの生体防御や炎症性腸疾患やアレルギー、急性GVDHなどの免疫異常の予防につながる可能性が高い。しかし、これまでILC3の細胞株は存在せず、gain-of functionによる生体内ILC3機能評価を行うことは不可能であった。本研究ではリンパ球の生存を促進させる恒常的活性型STAT5(STAT5CA) をレトロウイルスによりILC3へと遺伝子導入させ、ILC3細胞株の樹立を実現させるために必要なレトロウイルスベクターの樹立に成功した。
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