A study of microbiota activated regulatory B cells in inflammatory bowel diseases.
| Project/Area Number |
17K09382
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Shimane University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 腸内細菌 / 炎症性腸疾患 / 制御性免疫細胞 / 粘膜免疫 / Toll like receptor / 制御性B細胞 / IL-10 / Toll like recepter / 5 / 6 / 7 / 8 / 免疫学 / 自然免疫 |
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| Outline of Final Research Achievements |
Regulatory B cells (Breg) are involved in the pathogenesis of inflammatory bowel diseases. We investigated the molecular mechanisms how resident bacteria induce IL-10-producing Breg and ameliorate mucosal inflammation using several Toll-like receptor (TLR) knockout (KO) mice. B cells from TLR2 KO, but not TLR4 KO or TLR9 KO, mice produced low IL-10 in the presence of bacterial stimulation and failed to ameliorate T cell-mediated colitis. Next, we sought to determine the TLR2-dependent IL-10 production by microbiota-activated B cells. Western blotting indicated that a PI3K-AKT-GSK3B pathway is activated in the presence of TLR2 but not TLR4 stimulation. PI3Kp110d KO B cells were neither produce sufficient IL-10 when stimulated with bacteria nor ameliorated mucosal inflammation in vivo. These findings increase our understanding of the pathogenesis of IBD and regulation of mucosal homeostasis by resident microbiota.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の成果により、IBDの病態における腸内細菌を介したBreg誘導機構の一端を解明できたと考える。このシステムを応用し、生体内で効率的にBreg誘導ができるようになれば、安全で有効性のたかい新規のIBD治療法開発につながる可能性がある。難渋している現行のIBD治療とは異なるアプローチであり、実用化されれば臨床的意義は大きいと考える。
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Report
(4 results)
Research Products
(2 results)
