STAT5/Runx3 axis mediates cytotoxic activity in CD4+ T cells during early neuroinflammation

STAT5/Runx3 axis mediates cytotoxic activity in CD4+ T cells during early neuroinflammation | 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 STAT5/Runx3 axis mediates cytotoxic activity in CD4+ T cells during early neuroinflammation Alessandro Farias, Ana Marques, Fernando Pradella, Vinícius Boldrini, and 20 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7206354/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract CD4+ T cells are crucial for the development of autoimmune neuroinflammation in mice and are widely held to orchestrate the inflammatory cascade and immunopathology. Here, we show that auto-aggressive CD4⁺ T cells acquire a cytotoxic phenotype (CD4-CTL) and function during the early phase of relapsing-remitting multiple sclerosis (RRMS) and in experimental autoimmune encephalomyelitis (EAE). We identify the enhanced activation of the STAT5–Runx3 axis as a key driver of CD4-CTL development and maintenance. Notably, cytotoxic activity becomes more pronounced once these cells infiltrate the central nervous system (CNS). Importantly, a cytotoxic signature in peripheral CD4⁺ T cells reliably distinguishes early-stage RRMS patients from healthy controls. Mechanistically, CD4-CTLs share core molecular programs with effector CD8⁺ T cells. Together, our findings reveal potential biomarkers for early multiple sclerosis (MS) diagnosis, tools for monitoring treatment response, and targets for novel therapeutic strategies Biological sciences/Immunology/Neuroimmunology Biological sciences/Cell biology/Mechanisms of disease Full Text Additional Declarations (Not answered) Supplementary Files C1DAPI.jpg Figure 4f support material IM1Caspase.jpg Figure 4f support material IM1Myelin.jpg Figure 4f support material C1Myelin.jpg Figure 4f support material C1Caspase.jpg Figure 4f support material IM1DAPI.jpg Figure 4f support material Support4f.pdf Support Material 4f Marques2025FigS1.tif Figure S1 Marques2025FigS2.tif Figure S2 Marques2025FigS3.tif Figure S3 Marques2025FigS4.tif Figure S4 Marques2025FigS5.tif Figure S5 Marques2025FigS6.tif Figure S6 Cite Share Download PDF Status: Posted 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7206354","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":494845563,"identity":"ff9c8347-f03d-48a5-993f-4053ca337ee1","order_by":0,"name":"Alessandro 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