biostudies-literatureIzzy SU.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)U.S. Department of Defense (United States Department of Defense)499-516https://www.ebi.ac.uk/biostudies/studies/S-EPMC11893472biostudies-literatureUnknown28(3)Neuroinflammation plays a crucial role in traumatic brain injury (TBI), contributing to both damage and recovery, yet no effective therapy exists to mitigate central nervous system (CNS) injury and promote recovery after TBI. In the present study, we found that nasal administration of an anti-CD3 monoclonal antibody ameliorated CNS damage and behavioral deficits in a mouse model of contusional TBI. Nasal anti-CD3 induced a population of interleukin (IL)-10-producing regulatory T cells (T_reg cells) that migrated to the brain and closely contacted microglia. T_reg cells directly reduced chronic microglia inflammation and regulated their phagocytic function in an IL-10-dependent manner. Blocking the IL-10 receptor globally or specifically on microglia in vivo abrogated thNature neuroscienceNasal anti-CD3 monoclonal antibody ameliorates traumatic brain injury, enhances microglial phagocytosis and reduces neuroinflammation via IL-10-dependent T<sub>reg</sub>-microglia crosstalk.PMC11893472HT9425-24-1-06355K08NS123503-03Chopra KIzzy SPasquarelli-do-Nascimento GRezende RMBernstock JDBoucher MLMoreira TGda Silva PMontini FLu KJBrandao WNAlbastaki OWeiner HLLee JHAbou-El-Hassan HQuintana FJAronchik MDe Oliveira MGKrishnan RCarolina Durao AKaul MLanser TS LeServe DCao TBeauchamp LCButovsky OYahya TMannix RfalseNasal anti-CD3 monoclonal antibody ameliorates traumatic brain injury, enhances microglial phagocytosis and reduces neuroinflammation via IL-10-dependent T<sub>reg</sub>-microglia crosstalk.Neuroinflammation plays a crucial role in traumatic brain injury (TBI), contributing to both damage and recovery, yet no effective therapy exists to mitigate central nervous system (CNS) injury and promote recovery after TBI. In the present study, we found that nasal administration of an anti-CD3 monoclonal antibody ameliorated CNS damage and behavioral deficits in a mouse model of contusional TBI. Nasal anti-CD3 induced a population of interleukin (IL)-10-producing regulatory T cells (T_reg cells) that migrated to the brain and closely contacted microglia. T_reg cells directly reduced chronic microglia inflammation and regulated their phagocytic function in an IL-10-dependent manner. Blocking the IL-10 receptor globally or specifically on microglia in vivo abrogated th2025-01-01T00:00:00Z2025 Mar2025-04-22T11:14:33.438Z2025-04-05T23:53:41.076ZS-EPMC118934724001635310.1038/s41593-025-01877-7