| Project/Area Number |
18K15187
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 49070:Immunology-related
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| Research Institution | Osaka University |
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Principal Investigator |
Okumura Ryu 大阪大学, 医学系研究科, 助教 (00793449)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 粘膜バリア / 糖鎖 / 腸管上皮細胞 / 炎症性腸疾患 / 粘液 / 糖転移酵素 / 腸内細菌 / 腸管粘膜バリア |
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| Outline of Final Research Achievements |
In the gut, where tremendous numbers of bacteria exist, a large amount of mucus secreted by intestinal epithelial cells cover the gut epithelia to prevent bacteria from invading the intestinal tissue. The mucus contains high amounts of glycans, which are known to be critical for the function of the mucus. However, the mechanism by which the glycan expression is regulated and the details of the glycan functions in the gut remained unclear. In this study, we found that the expression of B3galt5 and St6galnac6, which are glycosyltransferases, is upregulated by commensal bacteria in the small intestine. In addition, it was found that these glycosyltransferases are highly and constitutively expressed in the large intestine. Finally, we found that the defect of disialyl lewis a in the gut, which is a glycan structure biosynthesized through the expression of B3galt5 and St6galnac6, resulted in high susceptibility to intestinal inflammation.
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| Academic Significance and Societal Importance of the Research Achievements |
潰瘍性大腸炎やクローン病に代表される炎症性腸疾患（以下IBD）は、いまだ根治的治療がない難治性疾患である。IBDの病因の一つして、腸管上皮によって構築される粘液を中心とした粘膜バリアの破綻が示唆されているが、その詳細は不明である。本研究によって腸管での機能が明らかとなったB3GALT5遺伝子は、一部のIBD患者でその遺伝子異常が報告されており、その異常はIBDの病因の一つである可能性がある。本研究ではB3galt5、St6galnaac6によって生合成されるジシアリルルイスAの粘膜バリアにおける重要性が明らかとなり、その糖鎖をターゲットとした新たな炎症性腸疾患治療が期待される。
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