{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kimura K"],"funding":["NEI NIH HHS","NIA NIH HHS","NIAID NIH HHS","NINDS NIH HHS"],"pagination":["718-731"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12079183"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["641(8063)"],"pubmed_abstract":["Microglia are the resident immune cells in the brain and have pivotal roles in neurodevelopment and neuroinflammation<sup>1,2</sup>. 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 disease<sup>3</sup>, and it can induce T cell exhaustion<sup>4</sup>. 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"],"journal":["Nature"],"pubmed_title":["Immune checkpoint TIM-3 regulates microglia and Alzheimer's disease."],"pmcid":["PMC12079183"],"funding_grant_id":["R01 AG054672","U19 AG069701","R21 AG076982","R01 EY027921","R01 NS088137","P30 AG066519","RF1 AG082704","R01 AG051812","R01 AG075509","P01 AI056299","P01 AI073748","R01 AG080992","R01 AI144166"],"pubmed_authors":["Aastha A","Liu L","Suhail A","Suva ML","Zhang H","Kimura K","Kleemann KL","Kuchroo VK","Subramanian A","Cheng Y","Ding X","Adhikari N","Lambden C","Silveira S","Guzchenko I","Tang R","Weiner HL","Gupta N","Wu Y","Khalilnezhad A","Singh V","Dixon KO","Rozenblatt-Rosen O","He D","Blurton-Jones M","Chitta UK","Yin Z","Nomura M","Cruchaga C","Freeman GJ","Durao A","Eskandari-Sedighi G","Delorey T","Myers SA","Regev A","Zhang X","Selkoe DJ","Barry JL","Pertel T","Butovsky O"],"additional_accession":[]},"is_claimable":false,"name":"Immune checkpoint TIM-3 regulates microglia and Alzheimer's disease.","description":"Microglia are the resident immune cells in the brain and have pivotal roles in neurodevelopment and neuroinflammation<sup>1,2</sup>. 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 disease<sup>3</sup>, and it can induce T cell exhaustion<sup>4</sup>. 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","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 May","modification":"2026-06-05T09:28:28.148Z","creation":"2026-05-15T03:12:44.822Z"},"accession":"S-EPMC12079183","cross_references":{"pubmed":["40205047"],"doi":["10.1038/s41586-025-08852-z"]}}