{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Navarro Negredo P"],"funding":["Simons Foundation","Human Frontier Science Program","NIA NIH HHS","Chinese Academy of Medical Sciences","NCRR NIH HHS","The Chan Zuckerberg Initiative","National Institutes of Health","Wellcome Trust","National Institute on Aging","NIH HHS"],"pagination":["458-476.e13"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12927632"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["59(2)"],"pubmed_abstract":["The immune system could play an important role in the age-related decline in brain function, yet specific immune-based strategies to enhance brain resilience in older individuals are lacking. Here, we combined engineered proteins and direct brain delivery to target immune cell populations within the old brain. We detected T cells with an exhaustion signature in the old brain and targeted them with a potent engineered checkpoint inhibitor (RIPR-PD1). This led to T cell expansion and strong pro-inflammatory responses in many brain cell types, notably microglia. To rescue age-related inflammatory imbalances in microglia, we used the anti-inflammatory cytokine interleukin (IL)-10. IL-10 boosted anti-inflammatory responses in old microglia, but it also triggered pro-inflammatory signaling. An e"],"journal":["Immunity"],"pubmed_title":["Targeting immune cells in the aged brain reveals that engineered cytokine IL-10 enhances neurogenesis and improves cognition."],"pmcid":["PMC12927632"],"funding_grant_id":["AG077816","S10 RR025518","S10RR027431-01","WT101609MA","F32 AG064823","R01AG071711","P01 AG036695","S10OD026831-01","AG064823","R01 AG071711","R01 AG077816","2018-I2M-2-002","S10RR025518-01","AG086042","S10 OD026831","F31 AG086042","S10 RR027431"],"pubmed_authors":["Xu L","Richard DJ","Brunet A","Garcia KC","Hauptschein M","Tsai AP","Picton L","Saxton RA","Abhiraman GC","Ramirez Lopez E","Schroer AB","Zhou OY","Wyss-Coray T","Ramirez-Matias J","You J","Fernandes RA","Buckley MT","Sun ED","Navarro Negredo P","Sucharov J","Villeda SA","Notarangelo G","Malacon KE"],"additional_accession":[]},"is_claimable":false,"name":"Targeting immune cells in the aged brain reveals that engineered cytokine IL-10 enhances neurogenesis and improves cognition.","description":"The immune system could play an important role in the age-related decline in brain function, yet specific immune-based strategies to enhance brain resilience in older individuals are lacking. Here, we combined engineered proteins and direct brain delivery to target immune cell populations within the old brain. We detected T cells with an exhaustion signature in the old brain and targeted them with a potent engineered checkpoint inhibitor (RIPR-PD1). This led to T cell expansion and strong pro-inflammatory responses in many brain cell types, notably microglia. To rescue age-related inflammatory imbalances in microglia, we used the anti-inflammatory cytokine interleukin (IL)-10. IL-10 boosted anti-inflammatory responses in old microglia, but it also triggered pro-inflammatory signaling. An e","dates":{"release":"2026-01-01T00:00:00Z","publication":"2026 Feb","modification":"2026-07-16T17:41:59.285Z","creation":"2026-07-09T11:09:35.515Z"},"accession":"S-EPMC12927632","cross_references":{"pubmed":["41619730"],"doi":["10.1016/j.immuni.2026.01.016"]}}