id_652. TYPE I INTERFERON SIGNALING SHAPES MICROGLIAL ACTIVATION AFTER ISCHEMIC BRAIN INJURY
Julia Jarco1,2, Alba Simats2,4, Natalia Małek1, Marta Kamińska3, Anna Planas2,4
1 Wroclaw University of Science and Technology, Department of Chemical Biology and Bioimaging, Wroclaw, Poland
2 Institute for Biomedical Research of Barcelona (IIBB) - Spanish Research Council (CSIC), Department of Neuroscience and Experimental Therapeutics, Barcelona, Spain
3 University of Bergen, Department of Clinical Science, Bergen, Norway
4 Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
INTRODUCTION: Ischemic stroke triggers a strong neuroinflammatory response involving resident microglia and infiltrating immune cells. Increasing evidence indicates that type I interferon (IFN-I)–related signaling pathways are activated in microglia following brain injury; however, the functional role of this response in shaping neuroimmune and immunometabolic processes remains unclear.
AIM(S): The aim of this study is to investigate the role of type I IFN signaling in microglial activation and immunometabolic responses following ischemic stroke, with particular focus on microglia–immune cell interactions within intact brain tissue.
METHOD(S): A mouse model of ischemic stroke was used, including genetically modified mice with ablation of the type I IFN receptor (IFNAR-deficient mice). Immune cells were isolated from brain tissue and analyzed using imaging mass cytometry and flow cytometry to characterize microglial activation states and spatial interactions with infiltrating immune populations at single-cell resolution.
RESULTS: Preliminary analyses indicate that ischemic brain injury is associated with distinct microglial activation patterns linked to IFN-I signaling. Spatial profiling reveals heterogeneous microglial states and region-specific interactions with infiltrating immune cells, suggesting a potential role for IFN-I pathways in shaping the post-stroke neuroimmune microenvironment.
CONCLUSIONS: These findings provide insight into the involvement of type I IFN signaling in microglial immunometabolic responses after ischemic stroke. Spatially resolved approaches enable the identification of neuroimmune features that may be inaccessible to dissociative methods and contribute to a better understanding of post-injury neuroinflammation.
FINANCIAL SUPPORT: This work was supported by MCIN/AEI/10.13039/501100011033 (grant PID2023-150949OB-I00) and by the National Science Centre (NCN), Poland (grants 2023/49/B/NZ7/02172 and 2023/05/Y/NZ4/00152).