Abstract 98: Brain-Derived Programmed Death-Ligand 1 Induces Post-Stroke Immunosuppression

Abstract

Background and purpose: Post-stroke immunosuppression is associated with increased infection risk and mortality of stroke patients. However, the mechanisms driving post-stroke immunosuppression are not fully elucidated and strategies to prevent this fatal complication are lacking. We investigated the role of programmed death-ligand 1 (PD-L1) on post-stroke lymphocyte deficiency in a murine model of intracerebral hemorrhage (ICH). Methods: ICH was induced by intracerebral injection of autologous blood or collagenase IV to male C57BL/6 (B6) mice. Mice were randomly assigned into two groups to received anti-PD-1 antibody and vehicle respectively via intraperitoneal injection operating at 1 hour after ICH. Neurological function assessment, immunofluorescence, Elisa, flow cytometry, lung colony calculated were analyzed. Results: In a mice model of ICH, we identified that neuron-derived programmed death ligand 1 (PD-L1) are downregulated and released to the blood post ICH. Increased PD-L1 induced T cell and NK cell deficiency via their expressed PD-1, which are associated with increased lung infection post-ICH. Blocking PD-L1 pathway via an anti-PD-1 monoclonal antibody prevented the spleen atrophy of ICH mice, and improved peripheral T and NK cell numbers and function. Anti PD-1 antibody treated mice showed improved clinical outcome and reduced pulmonary bacterial burden. Conclusions: This study identified brain-derived PD-L1 to the periphery as a new pathway that lead to post-stroke immunosuppression, targeting PD-L1 could be a potential treatment strategy to reduce post-stroke infection risk. Key words: Programmed death ligand 1,intracerebral hemorrhage, neuron,immunosuppression, inflammation Short title: PD-L1 and post-stroke immunosuppression