Interleukin-33 (IL-33) as cytokine released upon damages in tissue cells, is important for homeostasis regulation and immune response. In the central nervous system (CNS), IL-33 plays important functions, release as alarmin and pro-inflammatory mediator. During CNS development, astrocytic IL-33 refines synaptic circuitry via regulating microglial synapse engulfment. While in adult stages, activity-regulated astrocytic IL-33 secretion mediates synaptic homeostatic plasticity via modification of synapse number. Dysfunction of IL-33 signaling in CNS can lead to various neurodegenerative diseases such as Alzheimer’s disease (AD). Studies suggest IL33 as risk factor of AD, and with brain IL33 transcript level, serum and CSF IL-33 expression being lowered in AD individuals when compared with...[ Read more ]

Interleukin-33 (IL-33) as cytokine released upon damages in tissue cells, is important for homeostasis regulation and immune response. In the central nervous system (CNS), IL-33 plays important functions, release as alarmin and pro-inflammatory mediator. During CNS development, astrocytic IL-33 refines synaptic circuitry via regulating microglial synapse engulfment. While in adult stages, activity-regulated astrocytic IL-33 secretion mediates synaptic homeostatic plasticity via modification of synapse number. Dysfunction of IL-33 signaling in CNS can lead to various neurodegenerative diseases such as Alzheimer’s disease (AD). Studies suggest IL33 as risk factor of AD, and with brain IL33 transcript level, serum and CSF IL-33 expression being lowered in AD individuals when compared with normal controls. IL-33 treatment also reverses synaptic plasticity impairment, rescues memory deficit, and reduces β-amyloid accumulation in a transgenic mouse model of AD. However, the regulatory mechanism of IL-33 in astrocytes during AD cognitive decline is still unclear. In this study, I utilized a transgenic mouse model of AD – 5xFAD as study model. Based on the transcriptomic data, I identified the abundance of IL-33 expression in specific astrocyte subpopulation, showing enriched gene markers for synapse-related functions. Further investigation with mouse immunofluorescence staining data confirmed that under normal physiology, the expression of astrocytic IL-33 increased in hippocampal CA1 region but decreased in DG regions. While in AD, such astrocytic IL-33 level decreased in hippocampus and showed no correlation with beta-amyloid (Aβ) plaques. Therefore, understanding how hippocampal astrocytic IL-33 regulated during lifetime and neurodegeneration gain insight for elucidating synaptic dysregulation, providing foundation for astrocytic IL-33 as potential therapeutic target in AD pathology.