Type I IFN activates border-associated macrophages to drive MHC-I–dependent immune surveillance after stroke

Type I IFN activates border-associated macrophages to drive MHC-I–dependent immune surveillance after stroke | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Type I IFN activates border-associated macrophages to drive MHC-I–dependent immune surveillance after stroke Anna Planas, Jordi Pedragosa, Sara Figuerola, Maria Arbaizar-Rovirosa, and 13 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8563301/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Central nervous system border-associated macrophages (BAMs) reside at the interfaces of the cerebrospinal fluid, the brain parenchyma, and the vasculature, positioning them as key sensors of cerebrovascular injury. We examined the response of BAMs to ischemic stroke using mice engineered to report combined Cx3cr1 and Lyve1 expression. Stroke induced proliferation of embryonically derived BAMs and promoted their acquisition of a pro-inflammatory state along with MHC-I-mediated enhanced antigen presentation capabilities. MHC-I upregulation was driven by the delayed activation of a type-I interferon (IFN-I) program. Although CD8+ T cells were largely bystander-activated after stroke and infiltrated the brain in an antigen-independent manner, BAMs interacted with infiltrating CD8+ T cells in both mouse and human brains. Overall, the study shows that stroke reprograms BAMs into an IFN-I–driven, antigen presenting state that can enhance CD8+ T cell-mediated immune surveillance in the brain. Biological sciences/Neuroscience/Diseases of the nervous system/Stroke Biological sciences/Immunology/Inflammation Brain ischemia perivascular macrophages immunity translatome T cells mouse human stroke Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SuppDataS1.xls supporting data excel file SupportingblotsforFigure5.tif supporting blots for Figure 5 Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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