Furthermore, brain CD8 + T cells of APP-PS1 and aged WT mice showed similar differentially regulated genes as brain Trm CD8 + T cells in mouse models with acute virus infection, chronic parasite infection, and tumor growth. Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis on the significantly upregulated genes revealed overrepresentation of biological processes involved in IFN-β signaling and the response to viral infections. The gene signature of brain CD8 + T cells identified them as tissue-resident memory (Trm) T cells. Brain CD8 + T cells of APP-PS1 and WT animals had similar transcriptomic profiles and substantially differed from blood circulating CD8 + T cells. To gain further insights into the putative functions of CD8 + T cells in the brain, we explored and compared the transcriptomic profile of CD8 + T cells isolated from the brain and blood of transgenic AD (APPswe/PSEN1dE9, line 85 ) and age-matched wild-type (WT) mice. The functional properties of CD8 + T cells in the brain are largely unknown. As AD progresses, CD8 + T cells infiltrate into the brain parenchyma, where they tightly associate with neurons and microglia. Peripheral immune cell infiltration into the brain is a prominent feature in aging and various neurodegenerative diseases such as Alzheimer’s disease (AD).
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