Pathogenic CD8+ T cells target K71+ Henle’s layer by forming cytolytic immune synapses in Alopecia Areata

Pathogenic CD8+ T cells target K71+ Henle’s layer by forming cytolytic immune synapses in Alopecia Areata | 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 Pathogenic CD8+ T cells target K71+ Henle’s layer by forming cytolytic immune synapses in Alopecia Areata Rupali Gund, Jin Yong Kim, Valia Leifer, Eunice Lee, Eddy Wang, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9487026/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 CD8+ NKG2D+ T cells mediate hair follicle (HF) damage in Alopecia Areata (AA); however, the mechanisms and targets of T cell attack are not yet known. Here, we showed that CD8+ T cells penetrate the dermal sheath and epithelial layers of HF in AA and stop abruptly upon reaching Henle’s layer of the inner root sheath. CD8+ T cells assembled a cytolytic immune synapse (IS) with polarization of Lck kinase and convergence of granzyme B. The formation of IS and localization of caspase-8-dependent apoptosis in KRT71+ Henle’s layer of IRS pinpointed these cells as T cell targets in AA. Using direct visualization of in situ activity of pathogenic CD8+ T cells within AA-affected mice skin, we elucidated the molecular mechanism and target of CD8+ T cell cytotoxicity within HF in AA. Biological sciences/Immunology/Autoimmunity Biological sciences/Immunology/Translational immunology Health sciences/Diseases/Skin diseases Biological sciences/Drug discovery/Target identification Biological sciences/Immunology/Immunological disorders/Autoimmune diseases Full Text Additional Declarations There is NO Competing Interest. Supplementary Files supplementarytables14.pdf Table 1, Table 2, Table 3, Table 4 supplementaryfigures.pdf supplementary figure 1, supplementary figure 1 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. 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-9487026","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":631763424,"identity":"f6ae67b1-343e-4948-aa17-e25d0e246a2e","order_by":0,"name":"Rupali 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