Study of the anti-inflammatory roles of the exosomes from intestinal epithelial cells in sepsis via a paracrine effect
| Project/Area Number |
19K09392
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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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| Review Section |
Basic Section 55060:Emergency medicine-related
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| Research Institution | Mie University |
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Principal Investigator |
PARK Eun Jeong 三重大学, 医学系研究科, 准教授 (20644587)
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| Co-Investigator(Kenkyū-buntansha) |
川本 英嗣 三重大学, 医学部附属病院, 講師 (20577415)
島岡 要 三重大学, 医学系研究科, 教授 (40281133)
住吉 美穂 三重大学, 医学部附属病院, 助教 (50510971)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 腸管粘膜免疫 / T細胞 / 腸管上皮細胞 / エキソソーム / 細胞接着 / インテグリン / マイクロRNA / 敗血症 / 腸管上皮 / 細胞外小胞 / サイトカイン / 樹状細胞 / 盲腸結紮穿刺（CLP） / マクロファージ |
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| Outline of Research at the Start |
敗血症は感染などに起因する制御不能な全身性の炎症反応が、腸管を含む多臓器の機能不全を惹起するショック病態である。腸管上皮細胞は、炎症の波及により透過性亢進が惹起されるなど傷害を受ける標的細胞であると同時に、メディエーター分泌を介して免疫麻痺など敗血症重症化病態の形成にも関わる制御細胞としても機能する可能性が示唆されるが、その詳細なメカニズムは不明である。本研究では腸管上皮細胞の敗血症での炎症制御における役割を、エキソソーム機能に注目して検討する。
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| Outline of Final Research Achievements |
We have tested a possibility that functions of dendritic cells (DCs) are altered in sepsis, especially between different immune tissues. Using a sepsis model of cecal ligation and puncture (CLP), DCs were isolated from spleen and mesenteric lymph nodes (MLNs) and subjected to analyzing induction of T-cell activation. We have found that spleen DCs and MLN DCs display different activities in eliciting T cell immune responses (Darkwah et al. 2019 Biomedicines). In addition, we examined if intestinal epithelium-derived luminally released exosomes exhibit the capacity in regulating expressions of proinflammatory cytokines. As a result, we found that some of functional miRNAs were supposed to possess an ability to suppress expressions of TNF-alpha and IL-17A (Appiah et al. 2020 International Journal of Molecular Sciences).
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| Academic Significance and Societal Importance of the Research Achievements |
本研究課題で得られた研究成果は、敗血症での樹状細胞の免疫誘導機能が全身誘導組織と粘膜誘導組織にて異なる可能性の発見であり、この研究成果をベースにして、将来、免疫反応の促進もしく抑制を目指す免疫疾患治療に向けての新しい基盤研究の設計に寄与すると考えられる。また、敗血症腸管上皮由来のエキソソームを用いての研究成果においては、腸管上皮細胞エキソソームが腸管の局所組織だけでなく、敗血症に疲弊される他器官の組織に対しての抗炎症作用や症状緩和の効果のもつ可能性を提示したことに、本研究の科学的意義があると考えられる。
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Report
(4 results)
Research Products
(57 results)
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[Journal Article] Elevated plasma soluble PD-L1 levels in out-of-hospital cardiac arrest patients2021
Author(s)
Sumiyoshi Miho, Kawamoto Eiji, Nakamori Yuki, Esumi Ryo, Ikejiri Kaoru, Shinkai Toru, Akama Yuichi, Ito-Masui Asami, Imai Hiroshi, Gaowa Arong, Park Eun Jeong, Shimaoka Motomu
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Journal Title
Journal of Clinical Medicine
Volume: 10
Pages: 4188-4188
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Sepsis Induces Deregulation of IL-13 Production and PD-1 Expression in Lung Group 2 Innate Lymphoid Cells.2021
Author(s)
Akama Y, Park EJ, Satoh-Takayama N, Gaowa A, Ito A, Kawamoto E, Darkwah S, Appiah MG, Myint PK, Ohno H, Imai H, Shimaoka M.
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Journal Title
Shock
Volume: 55
Issue: 3
Pages: 357-370
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] The Lectin-Like Domain of Thrombomodulin Inhibits β1 Integrin-Dependent Binding of Human Breast Cancer-Derived Cell Lines to Fibronectin.2021
Author(s)
Kawamoto E, Nago N, Okamoto T, Gaowa A, Masui-Ito A, Akama Y, Darkwah S, Appiah MG, Myint PK, Obeng G, Ito A, Caidengbate S, Esumi R, Yamaguchi T, Park EJ, Imai H, Shimaoka M.
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Journal Title
Biomedicines
Volume: 9
Issue: 2
Pages: 162-162
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] The Role of Innate Lymphoid Cells in the Regulation of Immune Homeostasis in Sepsis-Mediated Lung Inflammation.2020
Author(s)
Akama Y, Park EJ, Satoh-Takayama N, Gaowa A, Ito A, Kawamoto E, Darkwah S, Appiah MG, Myint PK, Ohno H, Imai H, Shimaoka M.
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Journal Title
Diagnostics (Basel)
Volume: 10
Issue: 10
Pages: 808-808
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Anti-adhesive effects of human soluble thrombomodulin and its domains2019
Author(s)
Kawamoto Eiji、Nago Nodoka、Okamoto Takayuki、Gaowa Arong、Masui-Ito Asami、Sakakura Yosuke、Akama Yuichi、Soe Zay Yar、Prajuabjinda Onmanee、Darkwah Samuel、Appiah Michael G.、Myint Phyoe Kyawe、Obeng Gideon、Park Eun Jeong、Imai Hiroshi、Shimaoka Motomu
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Journal Title
Biochemical and Biophysical Research Communications
Volume: 511
Issue: 2
Pages: 312-317
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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