Heat-killed Lactobacillus johnsonii Directly Inhibits Th17 Cell Effector Function via Selective Translational Suppression

Heat-killed Lactobacillus johnsonii Directly Inhibits Th17 Cell Effector Function via Selective Translational Suppression | 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 Heat-killed Lactobacillus johnsonii Directly Inhibits Th17 Cell Effector Function via Selective Translational Suppression Xiaofeng Zhou, Chin-Ning Chen, Selga Jansons, Faye Sun, Kimberly Bonger, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8737086/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 Interleukin-17A (IL-17A)–producing Th17 cells are essential for mucosal host defense but also drive chronic inflammation and fibrosis when dysregulated. While commensal Lactobacillus species modulate Th17 responses through antigen-presenting cells, their direct effects on differentiated Th17 cells are poorly understood. We demonstrate that heat-killed Lactobacillus johnsonii XZ17 (HK Lj) directly suppresses IL-17A production in induced Th17 (iTh17) cells, independent of antigen-presenting cells. Unlike live L. johnsonii, which reduces IL-17A via environmental acidification and cell death, HK Lj preserves iTh17 viability. Mechanistically, HK Lj selectively inhibits IL-17A translation without altering Il17a or Rorc mRNA levels, global protein synthesis, or other cytokines like IL-10. This suppression is independent of Toll-like or C-type lectin receptor signaling. These findings reveal a previously unrecognized mechanism by which a commensal-derived stimulus directly regulates cytokine translation, positioning HK Lj as a potential immunomodulatory agent for targeting pathological IL-17A while maintaining T cell survival. Biological sciences/Immunology/Lymphocytes/T cells/CD4-positive T cells/T-helper 17 cells Biological sciences/Microbiology/Bacteria/Bacterial host response Full Text Additional Declarations There is NO Competing Interest. Supplementary Files 1112RS.pdf Reporting Summary 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-8737086","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":586474403,"identity":"dccd4297-aca2-406d-87be-c51fcca78b42","order_by":0,"name":"Xiaofeng 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While commensal Lactobacillus species modulate Th17 responses through antigen-presenting cells, their direct effects on differentiated Th17 cells are poorly understood. We demonstrate that heat-killed Lactobacillus johnsonii XZ17 (HK Lj) directly suppresses IL-17A production in induced Th17 (iTh17) cells, independent of antigen-presenting cells. Unlike live L. johnsonii, which reduces IL-17A via environmental acidification and cell death, HK Lj preserves iTh17 viability. Mechanistically, HK Lj selectively inhibits IL-17A translation without altering Il17a or Rorc mRNA levels, global protein synthesis, or other cytokines like IL-10. This suppression is independent of Toll-like or C-type lectin receptor signaling. 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