Immune checkpoint TIM-3 regulates microglia and Alzheimer's disease.

ABSTRACT: Microglia are the resident immune cells in the brain and have pivotal roles in neurodevelopment and neuroinflammation^1,2. This study investigates the function of the immune-checkpoint molecule TIM-3 (encoded by HAVCR2) in microglia. TIM-3 was recently identified as a genetic risk factor for late-onset Alzheimer's disease³, and it can induce T cell exhaustion⁴. However, its specific function in brain microglia remains unclear. We demonstrate in mouse models that TGFβ signalling induces TIM-3 expression in microglia. In turn, TIM-3 interacts with SMAD2 and TGFBR2 through its carboxy-terminal tail, which enhances TGFβ signalling by promoting TGFBR-mediated SMAD2 phosphorylation, and this process maintains microglial homeostasis. Genetic deletion of Havcr2 in m

SUBMITTER: Kimura K 

PROVIDER: S-EPMC12079183 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature