A study of the environmental factors for the development of inflammatory bowel disease
| Project/Area Number |
10671113
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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 |
General surgery
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| Research Institution | Osaka University |
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Principal Investigator |
INOUE Yoshifumi Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (10294076)
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| Co-Investigator(Kenkyū-buntansha) |
KIYONO Hiroshi Research Institute For Microbial Diseases Osaka University, Professor, 微生物病研究所, 教授 (10271032)
TAKAHASHI Ichirou Research Institute For Microbial Diseases Osaka University, Lectuer, 微生物病研究所, 講師 (20206791)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1998: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | inflammatory bowel disease / TCR α- / - mice / mucosal immune system / elemental diet / enteric flora / Bacteroides vulgatus |
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| Research Abstract |
A major pathogenic factor for the development of inflammatory bowel disease (IBD) is the breakdown of the intestinal homeostasis between the host mucosal immune system and the luminal microenvironment. To assess the potential influence of luminal antigens on the development of IBD, we fed TCR αィイD1-/-ィエD1 mice with elemental diet (ED). ED-fed TCR αィイD1-/-ィエD1 mice showed no pathological features of IBD and their aberrant mucosal B cell responses were suppressed. Similar numbers of CD4+, ββ T cell were developed in the colonic mucosa of ED-fed mice; however, Th2-type cytokine productions were lower than those seen in diseased regular diet (RD)-fed mice. The higher cytokine production in diseased RD-fed mice could be attributed to the high incidence of Bacteroides vulgatus (recovered in 80% of these mice), which can induce Th2-type responses of CD4ィイD1+ィエD1 ββ T cells with a dominant Vβ8 expression. In contrast, ED-fed TCR αィイD1-/-ィエD1 mice exhibited a diversification of Vβ usage of ββT cell populations from the dominant Vβ8 one associated with B. vulgatus in cecal flora to Vβ6, Vβ11, and Vβ14. Rectal administration of disease-free ED-fed mice with B. vulgatus resulted in the development of Th2-type CD4ィイD1+ィエD1, ββ T cells induced colitis. These findings suggest that the ED-induced alteration of intestinal microenvironments such as the enteric flora prevented the development of IBD in TCR αィイD1-/-ィエD1 mice via the immunological quiescence of CD4ィイD1+ィエD1, ββ T cells.
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Report
(3 results)
Research Products
(9 results)
