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Aged microglia promote peripheral T cell infiltration by reprogramming the microenvironment of neurogenic niches
Xiaotao Zhang1,2, Rui Wang1,2, Haoran Chen1
1Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China.
Background:
The immune cell compartment of the mammalian brain changes dramatically and peripheral T cells infiltrate the brain parenchyma during normal aging. However, the mechanisms underlying age-related T cell infiltration in the central nervous system remain unclear.
Results:
Chronic inflammation and peripheral T cell infiltration were observed in the subventricular zone of aged mice. Cell-cell interaction analysis revealed that aged microglia released CCL3 to recruit peripheral CD8+ memory T cells. Moreover, the aged microglia shifted towards a pro-inflammation state and released TNF-α to upregulate the expression of VCAM1 and ICAM1 in brain venous endothelial cells, which promoted the transendothelial migration of peripheral T cells. In vitro experiment reveals that human microglia would also transit to a chemotactic phenotype when treated with CSF from the elderly.
Conclusions:
Our research demonstrated that microglia play an important role in the aging process of brain by shifting towards a pro-inflammation and chemotactic state. Aged microglia promote T cell infiltration by releasing chemokines and upregulating adhesion molecules on venous brain endothelial cells.
