MicroRNAs -122 and -1247 restrain the pathogenicity of effector CD4+ T cells in autoimmune inflammation

MicroRNAs -122 and -1247 restrain the pathogenicity of effector CD4+ T cells in autoimmune inflammation | 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 MicroRNAs -122 and -1247 restrain the pathogenicity of effector CD4 + T cells in autoimmune inflammation Bruno Silva-Santos, Carolina Cunha, Paula Romero, Daniel Inácio, and 10 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4187285/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 A hallmark of autoimmune diseases like multiple sclerosis (MS) is an imbalance between CD4 + T cell subsets, namely pro-inflammatory T helper 1 (Th)1 and Th17 cells, and anti-inflammatory Foxp3 + regulatory cells (Treg). Here we investigated which and how microRNAs (miRNAs) regulate these CD4 + T cell subsets in a pre-clinical model of MS. We established a triple reporter mouse for Ifng , Il17 and Foxp3 , subjected it to experimental autoimmune encephalomyelitis (EAE), and identified the miRNomes of purified Th1, Th17 and Treg cells. We found that miR-122-5p and miR-1247 target specific sets of mRNAs to restrain Th17 cell proliferation and Th1 cell differentiation, respectively, thus impacting on the course or severity of EAE. Cytokine-regulated miR-122-5p and miR-1247 expression levels inversely associated with pathogenic gene signatures between lymphoid and central nervous systems, indicating that these miRNAs act as peripheral brakes to CD4 + T cell pathogenicity that are subverted in the inflamed target organ. Biological sciences/Immunology/Autoimmunity Biological sciences/Immunology/Lymphocytes/T cells/CD4-positive T cells Biological sciences/Immunology/Gene regulation in immune cells/miRNA in immune cells T helper subsets cytokines microRNAs autoimmunity Full Text Additional Declarations There is NO Competing Interest. Supplementary Files Cunhaetal.SupplementaryMaterials.pdf MicroRNAs -122 and -1247 restrain the pathogenicity of effector CD4+ T cells in autoimmune inflammation 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-4187285","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":285414370,"identity":"20f87bdf-a949-4f02-8e3f-984213396817","order_by":0,"name":"Bruno Silva-Santos","email":"data:image/png;base64,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","orcid":"https://orcid.org/0000-0003-4141-9302","institution":"Instituto de Medicina Molecular - João Lobo Antunes, Universidade de Lisboa","correspondingAuthor":true,"prefix":"","firstName":"Bruno","middleName":"","lastName":"Silva-Santos","suffix":""},{"id":285414371,"identity":"2c903f5e-b782-4837-8611-89c4959cf75e","order_by":1,"name":"Carolina Cunha","email":"","orcid":"","institution":"Instituto de Medicina Molecular","correspondingAuthor":false,"prefix":"","firstName":"Carolina","middleName":"","lastName":"Cunha","suffix":""},{"id":285414372,"identity":"f7b2618c-5f6e-460f-a6e5-a43649258fe1","order_by":2,"name":"Paula Romero","email":"","orcid":"","institution":"Instituto de Medicina Molecular","correspondingAuthor":false,"prefix":"","firstName":"Paula","middleName":"","lastName":"Romero","suffix":""},{"id":285414373,"identity":"75de53ad-7601-4e5b-8c87-b3443e644248","order_by":3,"name":"Daniel Inácio","email":"","orcid":"","institution":"Instituto de Medicina Molecular","correspondingAuthor":false,"prefix":"","firstName":"Daniel","middleName":"","lastName":"Inácio","suffix":""},{"id":285414374,"identity":"6f3e36ea-eef0-438b-9ca4-4c256fcc470f","order_by":4,"name":"Ana Pais","email":"","orcid":"","institution":"Instituto de Medicina Molecular","correspondingAuthor":false,"prefix":"","firstName":"Ana","middleName":"","lastName":"Pais","suffix":""},{"id":285414375,"identity":"59e096d5-dcbf-443a-91d6-b85417f82dba","order_by":5,"name":"Catarina Pelicano","email":"","orcid":"","institution":"Instituto de Medicina Molecular","correspondingAuthor":false,"prefix":"","firstName":"Catarina","middleName":"","lastName":"Pelicano","suffix":""},{"id":285414376,"identity":"6ffc652e-eb11-490f-b69b-4c91da3461b7","order_by":6,"name":"Marina Costa","email":"","orcid":"","institution":"Instituto de Medicina Molecular","correspondingAuthor":false,"prefix":"","firstName":"Marina","middleName":"","lastName":"Costa","suffix":""},{"id":285414377,"identity":"bf890550-e152-45cc-b547-3870bc14611b","order_by":7,"name":"Sofia Mensurado","email":"","orcid":"","institution":"Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa","correspondingAuthor":false,"prefix":"","firstName":"Sofia","middleName":"","lastName":"Mensurado","suffix":""},{"id":285414378,"identity":"0552660b-ad7f-4f45-b7c3-fe876ae5488b","order_by":8,"name":"Natacha Gonçalves-Sousa","email":"","orcid":"","institution":"Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa","correspondingAuthor":false,"prefix":"","firstName":"Natacha","middleName":"","lastName":"Gonçalves-Sousa","suffix":""},{"id":285414379,"identity":"1836f369-f09c-4c2d-90f0-2d67e816cd94","order_by":9,"name":"Pedro Papotto","email":"","orcid":"","institution":"Instituto de Medicina Molecular","correspondingAuthor":false,"prefix":"","firstName":"Pedro","middleName":"","lastName":"Papotto","suffix":""},{"id":285414380,"identity":"03f9bf02-1924-435c-a4bf-d2c3f49db04c","order_by":10,"name":"Daniel Neves","email":"","orcid":"","institution":"SGS Global Biosciences Center","correspondingAuthor":false,"prefix":"","firstName":"Daniel","middleName":"","lastName":"Neves","suffix":""},{"id":285414381,"identity":"ed834bc6-8062-4ab9-b45d-77ceb74f9aa4","order_by":11,"name":"Daniel Sobral","email":"","orcid":"https://orcid.org/0000-0003-3955-0117","institution":"National Institute of Health Doutor Ricardo Jorge","correspondingAuthor":false,"prefix":"","firstName":"Daniel","middleName":"","lastName":"Sobral","suffix":""},{"id":285414382,"identity":"c0392daf-d357-4280-8e25-7b9d060b5bd9","order_by":12,"name":"Francisco Enguita","email":"","orcid":"https://orcid.org/0000-0002-8072-8557","institution":"Instituto de Medicina Molecular João Lobo Antunes, Universidade de Lisboa","correspondingAuthor":false,"prefix":"","firstName":"Francisco","middleName":"","lastName":"Enguita","suffix":""},{"id":285414383,"identity":"5a80c964-ebfb-4af7-81da-3202a2765565","order_by":13,"name":"Anita Gomes","email":"","orcid":"","institution":"Instituto de Medicina Molecular","correspondingAuthor":false,"prefix":"","firstName":"Anita","middleName":"","lastName":"Gomes","suffix":""}],"badges":[],"createdAt":"2024-03-29 10:20:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4187285/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4187285/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":54383695,"identity":"29d3609d-c87a-4e5d-a72a-bb583499eb09","added_by":"auto","created_at":"2024-04-09 16:38:42","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1500601,"visible":true,"origin":"","legend":"","description":"","filename":"Cunhaetal.Manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4187285/v1_covered_6956bd3e-866c-4a01-82cb-d047ba0db964.pdf"},{"id":53828768,"identity":"64788512-4360-4d67-854c-23f759c37778","added_by":"auto","created_at":"2024-04-01 03:53:26","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":1360442,"visible":true,"origin":"","legend":"\u003cp\u003eMicroRNAs -122 and -1247 restrain the pathogenicity of effector CD4+ T cells in autoimmune inflammation\u003c/p\u003e","description":"","filename":"Cunhaetal.SupplementaryMaterials.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4187285/v1/5b76cded926194af6a2862e4.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"\u003cp\u003eMicroRNAs -122 and -1247 restrain the pathogenicity of effector CD4\u003csup\u003e+\u003c/sup\u003e T cells in autoimmune inflammation\u003c/p\u003e","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":"[email protected]","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":"T helper subsets, cytokines, microRNAs, autoimmunity","lastPublishedDoi":"10.21203/rs.3.rs-4187285/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4187285/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eA hallmark of autoimmune diseases like multiple sclerosis (MS) is an imbalance between CD4\u003csup\u003e+\u003c/sup\u003e T cell subsets, namely pro-inflammatory T helper 1 (Th)1 and Th17 cells, and anti-inflammatory Foxp3\u003csup\u003e+\u003c/sup\u003e regulatory cells (Treg). Here we investigated which and how microRNAs (miRNAs) regulate these CD4\u003csup\u003e+\u003c/sup\u003e T cell subsets in a pre-clinical model of MS. We established a triple reporter mouse for \u003cem\u003eIfng\u003c/em\u003e, \u003cem\u003eIl17\u003c/em\u003e and \u003cem\u003eFoxp3\u003c/em\u003e, subjected it to experimental autoimmune encephalomyelitis (EAE), and identified the miRNomes of purified Th1, Th17 and Treg cells. We found that miR-122-5p and miR-1247 target specific sets of mRNAs to restrain Th17 cell proliferation and Th1 cell differentiation, respectively, thus impacting on the course or severity of EAE. Cytokine-regulated miR-122-5p and miR-1247 expression levels inversely associated with pathogenic gene signatures between lymphoid and central nervous systems, indicating that these miRNAs act as peripheral brakes to CD4\u003csup\u003e+\u003c/sup\u003e T cell pathogenicity that are subverted in the inflamed target organ.\u003c/p\u003e","manuscriptTitle":"MicroRNAs -122 and -1247 restrain the pathogenicity of effector CD4+ T cells in autoimmune inflammation","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-01 03:53:21","doi":"10.21203/rs.3.rs-4187285/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","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":"55dc08ca-48ea-459b-a3e7-3263a5707e12","owner":[],"postedDate":"April 1st, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":30098275,"name":"Biological sciences/Immunology/Autoimmunity"},{"id":30098276,"name":"Biological sciences/Immunology/Lymphocytes/T cells/CD4-positive T cells"},{"id":30098277,"name":"Biological sciences/Immunology/Gene regulation in immune cells/miRNA in immune cells"}],"tags":[],"updatedAt":"2024-06-04T17:50:45+00:00","versionOfRecord":[],"versionCreatedAt":"2024-04-01 03:53:21","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4187285","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4187285","identity":"rs-4187285","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}