2021 Fiscal Year Annual Research Report
The role of B cell-derived secretory autophagosome-like vesicles in immune regulation
| Project/Area Number |
19K07606
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| Research Institution | Osaka University |
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Principal Investigator |
TSAI CHAO・YUAN 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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| Keywords | autophagy / autophagosome / extracelluar / vesicles / CD40 / IL-4 / B cell |
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| Outline of Annual Research Achievements |
Autophagy, which is known as an intracellular degradation system to support the cell homeostasis, is also involved in the unconventional secretion of cytosolic proteins. Since an autophagosome (Ap) marker, microtubule-associated protein 1A/1B-light chain 3 (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, the secretion of Ap-like EVs (ALVs) is still controversial and whether external stimulation can induce such secretion is unclear.
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. Live-imaging analysis reveals that intracellular fusion of AP-lysosome (L) is down-regulated in IL-4/CD40-stimulated B cells compared to IL-4/LPS-stimulated B cells. Additionally, autophagic flux is lower in IL-4/CD40-treated cells than in IL-4/LPS-treated cells. While IL-4/LPS signals induce the expression of genes involved in the AP-L fusion, IL-4/CD40 signals induce the expression of genes involved in the vesicular transportation. In regard to these results, we identify a small GTPase, Rab27a, is involved in the ALVs secretion. To further explore the physiological effects of B cell-derived ALVs on T cells in vitro, we find that ALVs enhance the proliferation of CD8+ T cells, but not CD4+ T cells. Moreover, LC3-II+ ALVs can be found in both mouse and human sera. Thus, our study may provide a new role of autophagy in regulating intercellular communication via ALVs in vivo.
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