The functional roles of IL-33/ST2 signaling in modulating microglial phenotypes in Alzheimer's disease

Abstract

Alzheimer’s disease (AD) is the most common form of dementia with no effective treatment nowadays. Emerging evidences suggest that microglia, the major type of immune cell in central nervous system, may contribute to AD pathogenesis. Subpopulation of microglia adopted a disease-associated/reactive state and skews away from homeostatic state along AD progression. While the disease-associated microglia (DAM) are co-localised with amyloid plaques, it remains unclear how the DAM subpopulation contribute to AD pathogenesis. We previously demonstrated that interleukin 33 (IL-33) administration rescues impaired cognitive functions and pathology in an AD transgenic mouse model, in part through enhancing amyloid phagocytosis by microglia. Here, we report that IL-33 administration regulates the gene signature of microglia in AD transgenic mice using single-cell RNA sequencing. While IL-33 administration did not significantly affect the proportion of homeostatic microglia in APP/PS1 mice, it modulates the transcriptome signature of DAM. Thus, our results collectively suggest that the transition of microglial state may play a role in mediating the beneficial effects of IL-33 in AD.

Date of Award	2018
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology