Microglial pattern recognition via IL-33 promotes synaptic refinement in developing corticothalamic circuits in mice.

ABSTRACT: Microglia are critical regulators of brain development that engulf synaptic proteins during postnatal synapse remodeling. However, the mechanisms through which microglia sense the brain environment are not well defined. Here, we characterized the regulatory program downstream of interleukin-33 (IL-33), a cytokine that promotes microglial synapse remodeling. Exposing the developing brain to a supraphysiological dose of IL-33 altered the microglial enhancer landscape and increased binding of stimulus-dependent transcription factors including AP-1/FOS. This induced a gene expression program enriched for the expression of pattern recognition receptors, including the scavenger receptor MARCO. CNS-specific deletion of IL-33 led to increased excitatory/inhibitory synaptic balance, spontaneous abs

SUBMITTER: Han RT 

PROVIDER: S-EPMC9757845 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature