{"paper_id":"27844a8d-b03f-4693-9c84-8c8ff0d9d7b6","body_text":"SLAMF9 activation by Akkermansia muciniphila-derived lipid LPE(16:0) drives IL-10+ B cell-mediated protection against ulcerative colitis | 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 SLAMF9 activation by Akkermansia muciniphila-derived lipid LPE(16:0) drives IL-10+ B cell-mediated protection against ulcerative colitis Ye Chen, Huiping Yang, Xuefeng Gao, Haolin Li, Shuze Chen, Lu Lin, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8143103/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 Ulcerative colitis (UC) pathogenesis involves aberrant interactions between the intestinal microbiota and immune system, notably reduced IL-10-producing B cells and diminished Akkermansia muciniphila (Akk). Probiotic extracellular vesicles (EVs) offer safety and transferability advantages over live bacteria. Here, we demonstrate that EVs from A. muciniphila (AkkEVs) reduce DSS-induced colitis by expanding IL-10+ B220+ cells. Lipidomics identified lysophosphatidylethanolamine (LPE(16:0)) as a lipid specifically enriched in AkkEVs. Mechanistically, LPE(16:0) binds SLAMF9 on B cells, activating the SAP/VAV1/ERK pathway to enhance IL-10 production and ameliorate colitis. Thus, AkkEVs and their derived lipid LPE(16:0) are novel SLAMF9 agonist and a candidate therapeutic for UC. Health sciences/Gastroenterology/Gastrointestinal diseases/Inflammatory bowel disease/Ulcerative colitis Biological sciences/Immunology/Adaptive immunity Biological sciences/Microbiology/Bacteria/Bacterial host response Ulcerative colitis Akkermansia muciniphila Extracellular vesicles LPE(16:0) IL-10-producing B cells SLAMF9 Full Text Additional Declarations There is NO Competing Interest. 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-8143103\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":true,\"archivedVersions\":[],\"articleType\":\"Article\",\"associatedPublications\":[],\"authors\":[{\"id\":550580894,\"identity\":\"3893ff7e-23ec-4e05-ad58-5c36d43b438f\",\"order_by\":0,\"name\":\"Ye Chen\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4UlEQVRIiWNgGAWjYDACCQglx8bMfvBBQkUN8VqM+dl5kg0enDlGvJbEmf0MZpIPW5gJ6+Cf3XzsMU8FA+OGwwxpFYkNbAz87d0J+C25cyzdmOcMA7PBYcZjNxJ3yDBInDm7Aa8WA4kcM2neNgY2A6AtNxLPsAFFcglpyf8mzfuPgQeoxawgsY2ZGC05bNK8DQwSks0MZgxEaZG4kWYmOecYgwE/M0+yRMKZYzwE/cI/I/mZxJsahvo2/uMHP/6oqJHjb+/FrwUEmHgY/sM5PASVgwDjD6KUjYJRMApGwYgFAKJzQlXGvgzuAAAAAElFTkSuQmCC\",\"orcid\":\"\",\"institution\":\"Shenzhen Hospital, Southern Medical University\",\"correspondingAuthor\":true,\"prefix\":\"\",\"firstName\":\"Ye\",\"middleName\":\"\",\"lastName\":\"Chen\",\"suffix\":\"\"},{\"id\":550580895,\"identity\":\"c9a2f95c-2c0f-488f-b924-7ad958888b38\",\"order_by\":1,\"name\":\"Huiping Yang\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"The Fifth Affiliated Hospital, Sun Yat-sen University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Huiping\",\"middleName\":\"\",\"lastName\":\"Yang\",\"suffix\":\"\"},{\"id\":550580896,\"identity\":\"cd1924bb-cbc4-4668-a95a-51fc298ab197\",\"order_by\":2,\"name\":\"Xuefeng Gao\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Shenzhen Hospital of Southern Medical University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Xuefeng\",\"middleName\":\"\",\"lastName\":\"Gao\",\"suffix\":\"\"},{\"id\":550580897,\"identity\":\"682fd066-26bb-45fd-b360-2392ab2c669f\",\"order_by\":3,\"name\":\"Haolin Li\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Nanfang Hospital, Southern Medical University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Haolin\",\"middleName\":\"\",\"lastName\":\"Li\",\"suffix\":\"\"},{\"id\":550580898,\"identity\":\"9e3b5e82-2210-4382-84e2-1f31d27fa4e9\",\"order_by\":4,\"name\":\"Shuze Chen\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Nanfang Hospital, Southern Medical University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Shuze\",\"middleName\":\"\",\"lastName\":\"Chen\",\"suffix\":\"\"},{\"id\":550580899,\"identity\":\"ab484b11-7e0e-4707-84ba-0fb8d80780de\",\"order_by\":5,\"name\":\"Lu Lin\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"The Fifth Affiliated Hospital, Sun Yat-sen University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Lu\",\"middleName\":\"\",\"lastName\":\"Lin\",\"suffix\":\"\"},{\"id\":550580900,\"identity\":\"6ecff018-00d3-43d9-9316-cf5ab8bb39e5\",\"order_by\":6,\"name\":\"Lei Mai\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"The Fifth Affiliated Hospital, Sun Yat-sen University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Lei\",\"middleName\":\"\",\"lastName\":\"Mai\",\"suffix\":\"\"},{\"id\":550580901,\"identity\":\"e936d023-b314-414a-b0e2-b97135d01f1a\",\"order_by\":7,\"name\":\"Ying Wang\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Shenzhen Hospital, Southern Medical University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Ying\",\"middleName\":\"\",\"lastName\":\"Wang\",\"suffix\":\"\"},{\"id\":550580902,\"identity\":\"91e84ca0-e3cc-44fe-aaf5-9ecf0304c9eb\",\"order_by\":8,\"name\":\"Xiuying Liu\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Shenzhen Hospital, Southern Medical University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Xiuying\",\"middleName\":\"\",\"lastName\":\"Liu\",\"suffix\":\"\"},{\"id\":550580903,\"identity\":\"3ce99edc-a4a4-4c7d-92dd-07a902b1ca6e\",\"order_by\":9,\"name\":\"Qiujuan Ye\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Nanfang Hospital, Southern Medical University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Qiujuan\",\"middleName\":\"\",\"lastName\":\"Ye\",\"suffix\":\"\"},{\"id\":550580904,\"identity\":\"22965665-97c9-45ea-8d35-4f6b6fc1b320\",\"order_by\":10,\"name\":\"Xiaofeng Li\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"The Fifth Affiliated Hospital, Sun Yat-sen University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Xiaofeng\",\"middleName\":\"\",\"lastName\":\"Li\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2025-11-18 08:46:08\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-8143103/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-8143103/v1\",\"draftVersion\":[],\"editorialEvents\":[],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":100358576,\"identity\":\"dcfbd980-d28c-4191-adc2-a5dc8c100149\",\"added_by\":\"auto\",\"created_at\":\"2026-01-16 07:21:10\",\"extension\":\"pdf\",\"order_by\":1,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":2723032,\"visible\":true,\"origin\":\"\",\"legend\":\"Article File\",\"description\":\"\",\"filename\":\"naturemicrobiology2025.11.141.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-8143103/v1_covered_a26f4a92-3205-46b5-91a3-ce44f1ac70e7.pdf\"}],\"financialInterests\":\"There is \\u003cb\\u003eNO\\u003c/b\\u003e Competing Interest.\",\"formattedTitle\":\"SLAMF9 activation by Akkermansia muciniphila-derived lipid LPE(16:0) drives IL-10+ B cell-mediated protection against ulcerative colitis\",\"fulltext\":[],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":false,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":true,\"hideJournal\":true,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":false,\"isAuthorSuppliedPdf\":true,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":true,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true},\"keywords\":\"Ulcerative colitis, Akkermansia muciniphila, Extracellular vesicles, LPE(16:0), IL-10-producing B cells, SLAMF9\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-8143103/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-8143103/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"Ulcerative colitis (UC) pathogenesis involves aberrant interactions between the intestinal microbiota and immune system, notably reduced IL-10-producing B cells and diminished Akkermansia muciniphila (Akk). Probiotic extracellular vesicles (EVs) offer safety and transferability advantages over live bacteria. Here, we demonstrate that EVs from A. muciniphila (AkkEVs) reduce DSS-induced colitis by expanding IL-10+ B220+ cells. Lipidomics identified lysophosphatidylethanolamine (LPE(16:0)) as a lipid specifically enriched in AkkEVs. Mechanistically, LPE(16:0) binds SLAMF9 on B cells, activating the SAP/VAV1/ERK pathway to enhance IL-10 production and ameliorate colitis. Thus, AkkEVs and their derived lipid LPE(16:0) are novel SLAMF9 agonist and a candidate therapeutic for UC.\",\"manuscriptTitle\":\"SLAMF9 activation by Akkermansia muciniphila-derived lipid LPE(16:0) drives IL-10+ B cell-mediated protection against ulcerative colitis\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2025-11-26 07:48:21\",\"doi\":\"10.21203/rs.3.rs-8143103/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"7ade8d33-2ab8-49f1-81fc-861d12b19c5e\",\"owner\":[],\"postedDate\":\"November 26th, 2025\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"posted\",\"subjectAreas\":[{\"id\":58582274,\"name\":\"Health sciences/Gastroenterology/Gastrointestinal diseases/Inflammatory bowel disease/Ulcerative colitis\"},{\"id\":58582275,\"name\":\"Biological sciences/Immunology/Adaptive immunity\"},{\"id\":58582276,\"name\":\"Biological sciences/Microbiology/Bacteria/Bacterial host response\"}],\"tags\":[],\"updatedAt\":\"2026-01-09T14:55:38+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2025-11-26 07:48:21\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-8143103\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-8143103\",\"identity\":\"rs-8143103\",\"version\":[\"v1\"]},\"buildId\":\"XKTyCvWXoU3ODBz1xrDgd\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}