| Project/Area Number |
14570453
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Gastroenterology
|
|---|
| Research Institution | Tokyo Medical and Dental University |
|---|
Principal Investigator |
NAKAMURA Tetsuya Tokyo Medical and Dental University, Department of Gastroenterology and Hepatology, Instructor, 大学院・医歯学総合研究科, 助手 (70265809)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
AZUMA Miyuki Tokyo Medical and Dental University, Department of Molecular Immunology, Professor, 大学院・医歯学総合研究科, 教授 (90255654)
KANAI Takanori Tokyo Medical and Dental University, Department of Gastroenterology and Hepatology, Assistant Professor, 医学部附属病院, 講師 (40245478)
WATANABE Mamoru Tokyo Medical and Dental University, Department of Gastroenterology and Hepatology, Professor, 大学院・医歯学総合研究科, 教授 (10175127)
TSUBATA Takeshi Tokyo Medical and Dental University, Medical Research Institute, Professor, 難治疾患研究所, 教授 (80197756)
ISHIKAWA Hiromichi Keio University, School of Medicine, Microbiology and Immunology, Professor, 医学部, 教授 (20051667)
|
|---|
| Project Period (FY) |
2002 – 2003
|
| Project Status |
Completed (Fiscal Year 2003)
|
| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2002: ¥2,400,000 (Direct Cost: ¥2,400,000)
|
|---|
| Keywords | IL-7 / IL-7 receptor / mucosal immunity / intestinal epithelial cell / transcriptional regulation / chronic colitis / IRF-1 / IRF-2 / Interferon Regulatory Factor-1 / Interferon Regulatory Factor-2 / 腸管粘膜免疫制御 / 遺伝子発現制御 / Interferon Regulatory Factor / 粘膜内リンパ球 / IL-7受容体 / TSLP |
|---|
| Research Abstract |
Our group has been focusing on the fundamental roles of intestinal epithelial cell-derived IL-7 and IL-7R-expressing lymphoid cells in local immune regulation within the gut. In this project, further attempts were made 1) to elucidate the regulatory mechanisms of IL-7 production in intestinal epithe-hal cells, and 2) to test whether elimination of IL-7R-expressing cells by toxin-conjugated anti-IL-7R antibodies might influence the pathogenesis of chronic colitis. We showed 1) that gene expression and protein production of JL-7 in intestinal epithelial cells are elegantly regulated by IRF family of tran-scription factors and also 2) that direct immunotoxin targeting of IL-7R caused significant ameliora-tion of chronic colitis in several model mice. These results not only provide a better understanding of the molecular mechanisms of mucosal immune regulation, but also propose the mucosal IL-7/IL-7R system to be a potential therapeutic target for a certain type of chronic colitis in humans.
|
