PhD candidate Nanyang Technological University Singapore, Singapore
Introduction/Rationale: The Polycomb group protein Ezh2 is an important epigenetic regulator that has been extensively studied for its role as an H3K27 methyltransferase in various biological mechanisms.
Methods: We utilize following techniques for the project: FACS, IF, Evans blue, Single cell analysis, QPCR
Results: Our preliminary data showed that Ezh2 deficiency in dendritic cells (DCs), the major professional antigen-presenting cells, leads to the accelerated thymic involution and an increase in CD8 T cells with a virtual memory phenotype (CD8 Tvm). In addition, mice with Ezh2-deficient DCs showed significant changes in CNS microglia and astrocytes. In details, distinct phenotypic changes were observed in microglia and astrocytes in the central nervous system (CNS) in mutant mice, indicative of an aging brain phenotype. Functional analysis revealed an activated and pro-inflammatory state in microglia from mutant mice, while astrocytes tended to promote blood-brain barrier disruption. Significant increases in several lymphocyte subsets, particularly CD8 Tvm, were observed both in the brain and in the blood circulation, suggesting its potential role in driving the observed brain aging phenotype. In addition, increased myeloid infiltration and Evans blue leakage in the brain of mutant mice indicates the blood-brain barrier disruption.
Conclusion: Further studies will elucidate the precise mechanisms of CD8 Tvm in the aging brain through their interaction with microglia and astrocytes. Collectively, these findings unravel the relationship between thymic involution and neuroinflammation, shed light on the potential impact of the CD8 Tvm cell subset on the CNS, and identify potential mediators of thymus-brain crosstalk.
