Lymphoid gene expression supports neuroprotective microglia function.

ABSTRACT: Microglia, the innate immune cells of the brain, play a defining role in the progression of Alzheimer's disease (AD)¹. The microglial response to amyloid plaques in AD can range from neuroprotective to neurotoxic². Here we show that the protective function of microglia is governed by the transcription factor PU.1, which becomes downregulated following microglial contact with plaques. Lowering PU.1 expression in microglia reduces the severity of amyloid disease pathology in mice and is linked to the expression of immunoregulatory lymphoid receptor proteins, particularly CD28, a surface receptor that is critical for T cell activation^3,4. Microglia-specific deficiency in CD28, which is expressed by a small subset of plaque-associated PU.1^low microgl

SUBMITTER: Ayata P 

PROVIDER: S-EPMC12675299 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature