Understanding the impact of gut inflammation-induced stress on hematopoiesis
| Project/Area Number |
18K16091
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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 54010:Hematology and medical oncology-related
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| Research Institution | Kumamoto University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 造血幹細胞 / 多能性前駆細胞 / 腸管炎症 / 腸内細菌 / 自然免疫 / TLRシグナル / 細胞分化 / 細胞遊走 / Bacteroides / Gr-1細胞 / 造血幹・前駆細胞 / 造血応答 / 炎症性老化 |
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| Outline of Final Research Achievements |
The previous report has shown that gram negative bacterial infection directly activates innate immune signaling in the dormant hematopoietic stem cells (HSCs) to induce proliferation and proliferative stress, eventually leading to functional impairment. Given as many commensal bacteria as human cells in our body, we hypothesized that microbial infiltration upon colitis might affect early hematopoiesis in bone marrow (BM). Then we tested this by employing dextran sulfate sodium (DSS)-induced colitis mouse model. Acute colitis expanded the hematopoietic stem and progenitor cells (HSPCs) in BM and the mesenteric lymph node, which is an inflammatory site. Acute colitis did not expand HSPCs of TRIF/Myd88-deficient mice in BM or MLN, indicating that HSPC expansion upon colitis is regulated via TLR signaling.
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| Academic Significance and Societal Importance of the Research Achievements |
“炎症と造血”は造血分野において近年ホットな研究領域であり、老化に伴い増加する炎症疾患との関連性だけでなく生体防御や組織損傷・修復における機能の観点からも注目を集めている分野である。本研究では炎症反応の起こる場である血液の幹細胞（造血幹細胞）をモデルとして、これまで明らかにされてこなかった腸管炎症下における腸内細菌依存的な造血応答制御を分子レベルで明らかにした。腸内細菌関連分子を新たな造血制御因子として捉えており、造血における新たなバイオロジーを提示したという点において、基礎医学への貢献は大きく学術的意義ならびに社会的意義の高い研究である。
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Report
(3 results)
Research Products
(14 results)
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[Journal Article] iPSC-Derived Platelets Depleted of HLA Class I Are Inert to Anti-HLA Class I and Natural Killer Cell Immunity.2020
Author(s)
Suzuki D, Flahou C, Yoshikawa N, Stirblyte I, Hayashi Y, Sawaguchi A, Akasaka M, Nakamura S, Higashi N, Xu H, Matsumoto T, Fujio K, Manz MG, Hotta A, Takizawa H, Eto K, Sugimoto N.
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Journal Title
Stem Cell Reports.
Volume: 14
Issue: 1
Pages: 49-59
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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