2022 Fiscal Year Annual Research Report
Functional analysis of astrocytes by using experimental autoimmune encephalomyelitis animal model (EAE)
| Project/Area Number |
20K16468
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| Research Institution | Juntendo University |
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Principal Investigator |
COSSU DAVIDE 順天堂大学, 健康総合科学先端研究機構, 准教授 (90867326)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | mitophagy / EAE / neuorinflammation / Parkin / Pink1 / astrocytes / microglia / BCG |
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| Outline of Annual Research Achievements |
Our recent research has shown that Parkin, an E3 ubiquitin ligase, modulates peripheral immune cells-mediated immunity during experimental autoimmune encephalomyelitis (EAE). Furthermore, we demonstrated that PTEN-induced putative kinase 1 (PINK1) protein, which acts upstream of Parkin in a common mitochondrial quality control pathway, plays an age-related role in modulating the peripheral inflammatory response during EAE, potentially contributing to the pathogenesis of neuroinflammatory and other associated conditions. The severity of EAE was associated with a significant increase in the frequency of dendritic cells, CD8+ lymphocytes, neutrophils, and a dysregulated cytokine profile in spleen, along with massive macrophage infiltration and activation of microglia and astrocytes in the spinal cord.
Furthermore, we demonstrated the efficacy of BCG Tokyo-172 vaccine in suppressing actively induced and spontaneous EAE models. Age-related neurorotection was associated with reduced proliferation of splenic T-cells, an elevated frequency of interleukin-10 secreting CD8+ T cells in the spleen and a polarization of microglia and astrocytes towards an anti-inflammatory phenotype.
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