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- W3016960412 abstract "Impairment of microglial clearance activity contributes to beta-amyloid (Aβ) pathology in Alzheimer’s disease (AD). While the transcriptome profile of microglia directs microglial functions, how the microglial transcriptome can be regulated to alleviate AD pathology is largely unknown. Here, we show that injection of interleukin (IL)-33 in an AD transgenic mouse model ameliorates Aβ pathology by reprogramming microglial epigenetic and transcriptomic profiles to induce a microglial subpopulation with enhanced phagocytic activity. These IL-33-responsive microglia (IL-33RMs) express a distinct transcriptome signature that is highlighted by increased major histocompatibility complex class II genes and restored homeostatic signature genes. IL-33-induced remodeling of chromatin accessibility and PU.1 transcription factor binding at the signature genes of IL-33RM control their transcriptome reprogramming. Specifically, disrupting PU.1-DNA interaction abolishes the microglial state transition and Aβ clearance that is induced by IL-33. Thus, we define a PU.1-dependent transcriptional pathway that drives the IL-33-induced functional state transition of microglia, resulting in enhanced Aβ clearance." @default.
- W3016960412 created "2020-04-24" @default.
- W3016960412 creator A5005602940 @default.
- W3016960412 creator A5010680026 @default.
- W3016960412 creator A5016023384 @default.
- W3016960412 creator A5022573698 @default.
- W3016960412 creator A5031867687 @default.
- W3016960412 creator A5038007210 @default.
- W3016960412 creator A5060875971 @default.
- W3016960412 date "2020-04-01" @default.
- W3016960412 modified "2023-10-17" @default.
- W3016960412 title "IL-33-PU.1 Transcriptome Reprogramming Drives Functional State Transition and Clearance Activity of Microglia in Alzheimer’s Disease" @default.
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