MRE11A Regulates Sepsis Through the mtDNA/STING Pathway of T Lymphocyte Apoptosis

MRE11A Regulates Sepsis Through the mtDNA/STING Pathway of T Lymphocyte Apoptosis | 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 Research Article MRE11A Regulates Sepsis Through the mtDNA/STING Pathway of T Lymphocyte Apoptosis Zhixin Wei, Feifei Wang, Pengji Qin, Zhiyong Yang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9414184/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 Objective and Significance : To analyze changes in meiosis-related recombination homolog 11A (MRE11A) expression in T lymphocytes from pediatric sepsis patients and mouse models, and to explore the potential regulatory mechanisms of MRE11A in sepsis. Methods : Flow cytometry was employed to detect MRE11A expression levels and the expression of the apoptosis-related molecule Cleaved Caspase-3 in peripheral blood T lymphocytes from 20 pediatric sepsis patients and 20 healthy control children. A mouse sepsis model was established via cecal ligation and puncture (CLP). Sepsis mice were treated at 24h, 48h, and 72h post-CLP. Intraperitoneal injection of the MRE11A inhibitor Mirin simulated reduced MRE11A expression in mice; Mirin-treated mice underwent processing 24h after inhibitor administration.CD3 + T cells were isolated from mouse spleens. Immunofluorescence was used to detect MRE11A expression in T lymphocyte cytoplasm. Real-time quantitative polymerase chain reaction (qPCR) assessed changes in mitochondrial DNA (mtDNA) within T lymphocyte cytoplasm. qPCR and Western blot (WB) analysis examined T lymphocyte expression of STING pathway-related factors cGAS,STING, and apoptosis-related factors, Cleaved Caspase-3, and Bax. Results :In the sepsis group, the proportion and expression levels of CD4 + MRE11A + T cells and CD8 + MRE11A + T cells were lower than those in the control group. The proportions of CD4 + Cleaved caspase-3 + T cells and CD8 + Cleaved caspase-3 + T cells were higher in the sepsis group than in the control group, with statistically significant differences between the two groups (both P < 0.05). MRE11A expression decreased in T cells from both the sepsis group (CLP24h, CLP72h) and the Mirin group, while mtDNA expression was upregulated (both P < 0.05).cGAS expression increased in T cells from sepsis group mice (CLP24h) and Mirin group mice, while STING expression was up-regulated in T cells from CLP48h and Mirin groups (all P < 0.05);T cells from the sepsis group (CLP24h, CLP48h) and Mirin group showed increased Cleaved Caspase-3 expression, while Bax expression was upregulated in CLP24h group T cells (all P < 0.05). Conclusions: MRE11A cytoplasmic expression was reduced in T lymphocytes from pediatric sepsis patients, potentially associated with T lymphocyte apoptosis. Low MRE11A expression in mouse sepsis T lymphocytes may induce mtDNA leakage, participating in T lymphocyte apoptosis by activating the cGAS/STING pathway.MRE11A may represent a novel therapeutic target for clinical treatment of sepsis. meiosis-related recombination 11 homolog A sepsis T lymphocytes apoptosis cGAS/STING pathway Full Text Additional Declarations No competing interests reported. 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-9414184","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":627783659,"identity":"d60181cf-7737-486d-a0c0-7257678a4098","order_by":0,"name":"Zhixin Wei","email":"","orcid":"","institution":"The First Affiliated Hospital of Guangxi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Zhixin","middleName":"","lastName":"Wei","suffix":""},{"id":627783660,"identity":"05563256-d474-49d4-9f45-59b8c40668b3","order_by":1,"name":"Feifei Wang","email":"","orcid":"","institution":"The First Affiliated Hospital of Guangxi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Feifei","middleName":"","lastName":"Wang","suffix":""},{"id":627783663,"identity":"5334b7ab-0e90-4984-80f4-a39286fb67e2","order_by":2,"name":"Pengji Qin","email":"","orcid":"","institution":"The First Affiliated Hospital of Guangxi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Pengji","middleName":"","lastName":"Qin","suffix":""},{"id":627783664,"identity":"652b77fc-bb04-4d93-9202-854135d6d062","order_by":3,"name":"Zhiyong Yang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABAUlEQVRIiWNgGAWjYBACgwNAgrFBAsRmfAATJFoLM0wpfi2SDWAtYDabBFFa+NnPHn75c4dFYr90+7XKr23bEhvYm7dJMNTcwamFjScvzULyjETizDlnym7LnLmd2MBzrEyC4dgz3FoYcswMDNskEjfcyEm7LVEB1CKRYybB2HAYtxb+N2YGiVAtxRIGQC3ybwhokcgxfnAQrCX9GOMHsC08hLS8MWNsbJMwnjkjh1ma4cxt4zaetGKLhGP4HJZj/PFnW51sv0T6QyDjtmw/++GNNz7U4NbCAI0OxwYGHgNmHnCAAEECPg3ASP8AJOwZGNgfMP7Ar3IUjIJRMApGKAAAEsZZxuHc0sUAAAAASUVORK5CYII=","orcid":"","institution":"The First Affiliated Hospital of Guangxi Medical University","correspondingAuthor":true,"prefix":"","firstName":"Zhiyong","middleName":"","lastName":"Yang","suffix":""}],"badges":[],"createdAt":"2026-04-14 10:26:54","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9414184/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9414184/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":107869737,"identity":"8028a20e-49b2-4ee8-aec0-dc60b9315ff7","added_by":"auto","created_at":"2026-04-27 07:38:02","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":940148,"visible":true,"origin":"","legend":"","description":"","filename":"SCI.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9414184/v1_covered_c39be46e-f302-4757-b44d-cfabd10b59f9.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"MRE11A Regulates Sepsis Through the mtDNA/STING Pathway of T Lymphocyte Apoptosis","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"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":"meiosis-related recombination 11 homolog A, sepsis, T lymphocytes, apoptosis, cGAS/STING pathway","lastPublishedDoi":"10.21203/rs.3.rs-9414184/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9414184/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective and Significance\u003c/strong\u003e: To analyze changes in meiosis-related recombination homolog 11A (MRE11A) expression in T lymphocytes from pediatric sepsis patients and mouse models, and to explore the potential regulatory mechanisms of MRE11A in sepsis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: Flow cytometry was employed to detect MRE11A expression levels and the expression of the apoptosis-related molecule Cleaved Caspase-3 in peripheral blood T lymphocytes from 20 pediatric sepsis patients and 20 healthy control children. A mouse sepsis model was established via cecal ligation and puncture (CLP). Sepsis mice were treated at 24h, 48h, and 72h post-CLP. Intraperitoneal injection of the MRE11A inhibitor Mirin simulated reduced MRE11A expression in mice; Mirin-treated mice underwent processing 24h after inhibitor administration.CD3 + T cells were isolated from mouse spleens. Immunofluorescence was used to detect MRE11A expression in T lymphocyte cytoplasm. Real-time quantitative polymerase chain reaction (qPCR) assessed changes in mitochondrial DNA (mtDNA) within T lymphocyte cytoplasm. qPCR and Western blot (WB) analysis examined T lymphocyte expression of STING pathway-related factors cGAS,STING, and apoptosis-related factors, Cleaved Caspase-3, and Bax.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e:In the sepsis group, the proportion and expression levels of CD4 + MRE11A + T cells and CD8 + MRE11A + T cells were lower than those in the control group. The proportions of CD4 + Cleaved caspase-3 + T cells and CD8 + Cleaved caspase-3 + T cells were higher in the sepsis group than in the control group, with statistically significant differences between the two groups (both P \u0026lt; 0.05). MRE11A expression decreased in T cells from both the sepsis group (CLP24h, CLP72h) and the Mirin group, while mtDNA expression was upregulated (both P \u0026lt; 0.05).cGAS expression increased in T cells from sepsis group mice (CLP24h) and Mirin group mice, while STING expression was up-regulated in T cells from CLP48h and Mirin groups (all P \u0026lt; 0.05);T cells from the sepsis group (CLP24h, CLP48h) and Mirin group showed increased Cleaved Caspase-3 expression, while Bax expression was upregulated in CLP24h group T cells (all P \u0026lt; 0.05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eMRE11A cytoplasmic expression was reduced in T lymphocytes from pediatric sepsis patients, potentially associated with T lymphocyte apoptosis. Low MRE11A expression in mouse sepsis T lymphocytes may induce mtDNA leakage, participating in T lymphocyte apoptosis by activating the cGAS/STING pathway.MRE11A may represent a novel therapeutic target for clinical treatment of sepsis.\u003c/p\u003e","manuscriptTitle":"MRE11A Regulates Sepsis Through the mtDNA/STING Pathway of T Lymphocyte Apoptosis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-24 13:51:43","doi":"10.21203/rs.3.rs-9414184/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":"2c98b590-0de0-4919-88cc-964f88676674","owner":[],"postedDate":"April 24th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-04-25T05:39:34+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-24 13:51:43","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9414184","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9414184","identity":"rs-9414184","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}