Development of novel therapy targeting dendritic cells for Crohn's disease
| Project/Area Number |
15590685
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Keio University |
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Principal Investigator |
IWAO Yasushi Keio University, Department of Medicine, Assistant Professor, 医学部, 講師 (40168547)
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| Co-Investigator(Kenkyū-buntansha) |
HIBI Toshifumi Keio University, Department of Medicine, Professor, 医学部, 教授 (50129623)
WATANABE Mamoru Tokyo Medical & Dental University, Dept of Medicine, Professor, 医学部, 教授 (10175127)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Crohn's disease / dendritic cell / natural killer T cell / antigen / inflammatory bowel disease / Th1 / Th2 |
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| Research Abstract |
Crohn's disease(CD) is a chronic inflammatory process involving the gastrointestinal tract, characterised by discontinuous and transmural inflammation. Although the etiology of CD is not fully understood, accumulating evidence suggests that dysregulation of the local immune system is pivotal in the pathogenesis of CD. Studies from humans and experimental murine colitis models indicate that in CD, the local immune response tends to be predominantly T helper cell type 1(Th1) and is reflected by local release of cytokines such as tumor necrosis factor (TNF)-□, interleukin (IL)-12, and IL-18. However, it has not been elucidated what triggers the Th1 immune response in CD. In the present study, we attempted to establish the purification of dendrtic cells from mesenteric lymph nodes(MLN) and to analyze the immune cascade in the mesenteric lymph nodes of human CD.
We established the purification of dendrtic cells from MLN by density gradient centrifugation and immunomagnetic depletion of CD3^+,CD11b^+ and CD16^+ cells followed by positive isolation with CD4^+. The analysis of cells obtained from MLNs revealed that the proportion of DC1 was increased in the MLN of CD compared to ulcerative colitis and control and that CD4+ T lymphocytes from the MLN of CD show a Th1 profile.
This is the first study to report the characterization of MLN dendritic cells and cytokine profiles of the MLN CD4+ T cells from human IBD patients. This study shows that MLN dendritic cells have considerable effects in the pathogenesis of IBD. The MLN may be the place where the dysregulated immune responses, such as Th1 in CD, first occur.
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Report
(3 results)
Research Products
(24 results)
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[Journal Article] T-bet up-regulation and subsequent interleukin 12 stimulation are essential for the induction of Th1 mediated immunopathology in Croha's disease.2004
Author(s)
Matsuoka K, Inoue N, Sato T, Okamoto S, Hisamatsu T, Kishi Y, Sakuraba A, Hitotsumatsu O, Fukushima T, Kanai T, Watanabe M, Ishii H, Hibi T
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Journal Title
Gut 53(9)
Pages: 1303-1308
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Human intestinal epithelial cell-derived interleukin(IL)-18, along with IL-2, IL-7 and IL-15, is a potent synergistic factor for the proliferation of intraepithelial lymphocytes.2004
Author(s)
Okazawa A, Kanai T, Nakamaru K, Sato T, Inoue N, Ogata H, Jwao Y, Ikeda M, Kawamura T, Makita S, Uraushihara K, Okamoto R, Yamazaki M, Kurimoto M, Ishii H, Watanabe M, Hibi T
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Journal Title
Clin Exp Immunol 136(2)
Pages: 269-276
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Hyperexpression of inducible costimulator and its contribution on lamina propria T cells in inflammatory bowel disease.2004
Author(s)
Sato T, Kanai T, Watanabe M, Sakuraba A, Okamoto S, Nakai T, Okazawa A, Inoue N, Totsuka T, Yamazaki M, Kroczek RA, Fukushima T, Ishii H, Hibi T
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Journal Title
Gastroenterology 126(3)
Pages: 829-839
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Contrasting action of IL-12 and IL-15 in the development of dextran sodium sulfate colitis in mice.2003
Author(s)
Takagi T, Kanai T, Okazawa A, Sato T, Takaishi H, Inoue N, Ogata H, Hoshino K, Takeda K, Akira S, Watanabe M, Jshii H, Hibi T
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Journal Title
Scand J Gastroenterol 38(8)
Pages: 837-844
Description
「研究成果報告書概要(欧文)」より
Related Report
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