Development of novel therapy targeting innate immunity for Crohn's disease
| Project/Area Number |
17590678
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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) |
WATANABE Mamoru Tokyo Medical & Dental University, Dept of Medicine, Professor, 医学部, 教授 (10175127)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2005: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Crohn's disease / dendritic cell / macrophage / innate immunity / inflammatory bowel disease / Th1 / Th2 |
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| Research Abstract |
Crohn's disease (CD) is a chronic inflammatory process involving the gastrointestinal tract, characterized 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)-α, 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 dendritic 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 dendritic 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.
Furthermore, we tried to elucidate the roles of macrophages in intestinal inflammation by using an IL-10-deficient (IL-10-/-) mouse colitis model, and demonstrated that abnormally differentiated subsets of intestinal macrophage play a key role in Th1-dominant chronic colitis through excess production of IL-12 and IL-23 in response to bacteria. These data provide new insights into the intestinal macrophages to gut flora relationship in the development of colitis in IL-10-/- mice.
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Report
(3 results)
Research Products
(19 results)
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[Journal Article] Cytomegalovirus is frequently reactivated and disappears without antiviral agents in ulcerative colitis patients.2007
Author(s)
Matsuoka K, Iwao Y, Mori T, Sakuraba A, Yajima T, Hisamatsu T, Okamoto S, Morohoshi Y, Izumiya M, Ichikawa H, Sato T, Inoue N, Ogata H, Hibi T
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Journal Title
Am J Gastroenterol 102(2)
Pages: 331-337
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] A New Technique for Endoscopic Submucosal Dissection for Early Gastric Cancer using an External Grasping Forceps.2006
Author(s)
Imaeda H, Iwao Y, Ogata H, Ichikawa H, Mori M, Hosoe N, Masaoka T, Nakashita M, Suzuki H, Inoue N, Aiura K, Nagata H, Kumai K, Hibi T
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Journal Title
Endoscopy. 38(10)
Pages: 1007-1010
Description
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[Journal Article] Inhibition of neutrophil elastase prevents the development of murine dextran sulfate sodium-induced colitis.2006
Author(s)
Morohoshi Y, Matsuoka K, Chinen H, Kamada N, Sate T, Hisamatsu T, Okamoto S, Inoue N, Takaishi H, Ogata H, Iwao Y, Hibi T
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Journal Title
J Gastroenterol 41(4)
Pages: 318-324
NAID
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Increase of bone marrow-derived secretory lineage epithelial cells during regeneration in the human intestine.2005
Author(s)
Matsumoto T, Okamoto R, Yajima T, Mori T, Okamoto S, Ikeda Y, Mukai M, Yamazaki M, Oshima S, Tsuchiya K, Nakamura T, Kanai T, Okano H, Inazawa J, Hibi T, Watanabe M
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Journal Title
Gastroenterology 127(7)
Pages: 1851-1867
Description
「研究成果報告書概要(欧文)」より
Related Report
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