| Project/Area Number |
19K07606
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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 49070:Immunology-related
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| Research Institution | Osaka University |
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Principal Investigator |
TSAI CHAOYUAN 大阪大学, 免疫学フロンティア研究センター, 特任助教(常勤) (10727001)
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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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | Autophagy / autophagosome / extracellular / vesicles / CD40 / IL-4 / B cell / autophagy / extracelluar / B cells / Secretory / IL-4/CD40 signaling / Immune regulation / Autophagosome / Extracellualr vesicles / ALVs / Secretory vesicles / Autophagosomes / Extracellular vesicles / intercellular network |
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| Outline of Research at the Start |
Autophagy is known as an intracellular degradation system. Our proposed research may reveal an important role of secretory autophagy in the immune network, which is different from previous reported, such as LC3-associated phagocytosis and autophagy-mediated cytokine maturation and secretion.
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| Outline of Final Research Achievements |
Autophagy is known as an intracellular degradation system to support the cellular homeostasis. Since an autophagosome (Ap) marker, LC3-II, could be found in the cell-derived extracellular vesicles (EVs) in vitro, autophagy may play a role during cell-to-cell communication. However, whether external signals induce the secretion of Ap-like EVs (ALVs) remains unknown.
Here, we demonstrate that IL-4 plus anti-CD40 antibodies (IL-4/CD40), but not IL-4 plus LPS (IL-4/LPS) induces the secretion of LC3-II+ ALVs in B cells. Additionally, the secretion of ALVs by IL-4/CD40 signals was regulated by a small GTPase, Rab27a. Furthermore, B cell-derived ALVs enhance the proliferation of CD8+ T cells, but not CD4+ T cells, in vitro. Importantly, LC3-II+ ALVs can be found in both mouse and human sera. Thus, we provide the first evidence that external signals induce the ALVs secretion in B cells and the ALVs may regulate the CD8+ T cell functions in vivo.
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| Academic Significance and Societal Importance of the Research Achievements |
After Yoshinori Ohsumi won the 2016 Nobel Prize for his discoveries of mechanisms for autophagy, fully understanding the functions of autophagy becomes emerging. Our findings extend the present knowledge of autophagy in regulating not only cellular homeostasis but also intercellular communication.
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