Synthesis of lipooligosaccharides partial structures including 2,3-diaminoglucose disaccharide skeleton for the elucidation of autoimmune disease onset mechanism
Project/Area Number |
16K01914
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Biomolecular chemistry
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Research Institution | Osaka University |
Principal Investigator |
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | リピドA / Campylobacter jejuni / 自己免疫疾患 / 2,3-ジアミノグルコース / アジュバント / ケミカルエコロジー / リポオリゴ糖 / 分子相同性 / 自然免疫 / ガングリオシド / ジアミノグルコース / 免疫 / リポ多糖 / 複合糖質 / 糖化学 |
Outline of Final Research Achievements |
A Gram negative bacteria, Campylobacter jejuni produces lipooligosaccharide (LOS) as an extracellular membrane component. LOS is composed of oligosaccharide and glycolipid “lipid A”, which is recognized by TLR4/MD-2 complex to regulate innate immunity. Since C. jejuni oligosaccharides have molecular homology with gangliosides in human nervous tissues, they can induce cross-reaction to cause autoimmune diseases. However, Helicobacter pylori having the same molecular homology does not induce cross-reaction. Therefore, we focused on the immune activity of LOS as other factor related to autoimmune diseases, and thus synthesized its lipid As and identified the active core structure of C. jejuni LOS.
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Academic Significance and Societal Importance of the Research Achievements |
リピドAは、抗原の免疫原性を高め抗体産生等の獲得免疫系の活性化を促進するアジュバント作用を有しており、C. jejuniリピドAが、自己免疫疾患発症における免疫交差反応の誘導に関与していることは確実である。しかしながら、特殊な2,3-ジアミノグルコース骨格を含むC. jejuniリピドAの合成例はこれまでになく、その機能は未解明であった。本研究において世界初の合成が達成されたC. jejuniリピドAの機能解析研究は、自己免疫疾患発症機構の解明や新規ワクチンアジュバント開発へと発展する可能性が高く、学術的にも社会的も意義深く十分な貢献が期待できると考えている。
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Report
(4 results)
Research Products
(118 results)
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[Journal Article] Lymphoid tissue-resident Alcaligenes LPS induces IgA production without excessive inflammatory responses via weak TLR4 agonist activity2018
Author(s)
N. Shibata, J. Kunisawa, K. Hosomi, Y. Fujimoto, K. Mizote, N. Kitayama, A. Shimoyama, H. Mimuro, S. Sato, N. 5 Kishishita, K. J. Ishii, K. Fukase, and H. Kiyono
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Journal Title
Mucosal Immunology
Volume: -
Issue: 3
Pages: 693-702
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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