{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:53:44Z","timestamp":1790834024659,"version":"4.1.0"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,13]],"date-time":"2022-09-13T00:00:00Z","timestamp":1663027200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Exosomes carry various types of transcripts, such as messenger RNAs (mRNAs), and play an important role in mediating cell-to-cell communication, thus influencing multiple physiological and pathological processes. However, the role of exosomal mRNAs in T1DM is largely unknown. Here, we aimed to identify the plasma-derived exosomal mRNA expression profiles in T1DM and to explore their potential biological functions in T1DM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>Plasma-derived exosomes were isolated from 10 patients with T1DM and 10 age- and sex-matched control subjects by size exclusion chromatography methods. Transmission electron microscopy, nanoparticle tracking analysis, and western blot analysis confirmed the presence of exosomes. The exosomal mRNAs were analyzed using the Illumina HiSeq platform. Six differentially expressed mRNAs (DEMs) were randomly selected to determine the expression level by quantitative real-time PCR (qRT\u2212PCR) in a larger cohort (T1DM subjects N=40; control subjects N=40). The biological functions of DEMs were predicted by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Protein\u2212protein interaction networks were constructed to explore the potential associations among DEMs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In total, 112 DEMs were identified in T1DM, among which 66 mRNAs were upregulated and 46 mRNAs were downregulated. Four of six candidate exosomal mRNAs were successfully validated by qRT\u2212PCR. Bioinformatics analysis indicated that these mRNAs were most significantly involved in positive regulation by host viral transcription (GO enrichment analysis) and oxidative phosphorylation (KEGG pathway analysis).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study reported the plasma-derived exosomal mRNA expression profiles of T1DM for the first time. The identified DEMs might be associated with the pathogenesis of T1DM, and some DEMs have the potential to serve as biomarkers and therapeutic targets for T1DM.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2022.995610","type":"journal-article","created":{"date-parts":[[2022,9,13]],"date-time":"2022-09-13T05:18:58Z","timestamp":1663046338000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["Plasma-derived exosomal mRNA profiles associated with type 1 diabetes mellitus"],"prefix":"10.3389","volume":"13","author":[{"given":"Wenqi","family":"Fan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haipeng","family":"Pang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiajie","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yimeng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuoming","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibo","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiguo","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiguang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31320-5","article-title":"Type 1 diabetes","volume":"391","author":"DiMeglio","year":"2018","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","first-page":"107842","DOI":"10.1016\/j.diabres.2019.107842","article-title":"Worldwide estimates of incidence, prevalence and mortality of type 1 diabetes in children and adolescents: Results from the international diabetes federation diabetes atlas, 9th edition","volume":"157","author":"Patterson","year":"2019","journal-title":"Diabetes Res Clin Pract"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.00119","article-title":"Advances in knowledge of candidate genes acting at the beta-cell level in the pathogenesis of T1DM","volume":"11","author":"Pang","year":"2020","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-019-0254-y","article-title":"The heterogeneous pathogenesis of type 1 diabetes mellitus","volume":"15","author":"Ilonen","year":"2019","journal-title":"Nat Rev Endocrinol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/nri855","article-title":"Exosomes: Composition, biogenesis and function","volume":"2","author":"Thery","year":"2002","journal-title":"Nat Rev Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1596","article-title":"Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells","volume":"9","author":"Valadi","year":"2007","journal-title":"Nat Cell Biol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.593348","article-title":"Emerging roles of exosomes in T1DM","volume":"11","author":"Pang","year":"2020","journal-title":"Front Immunol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.3107","article-title":"Exosomes and diabetes","volume":"35","author":"Castano","year":"2019","journal-title":"Diabetes Metab Res Rev"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-020-00443-4","article-title":"Type 1 diabetes mellitus as a disease of the beta-cell (do not blame the immune system)","volume":"17","author":"Roep","year":"2021","journal-title":"Nat Rev Endocrinol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.2337\/db16-0671","article-title":"Primary human and rat beta-cells release the intracellular autoantigens GAD65, IA-2, and proinsulin in exosomes together with cytokine-induced enhancers of immunity","volume":"66","author":"Cianciaruso","year":"2017","journal-title":"Diabetes"},{"key":"B11","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1016\/j.cmet.2018.09.011","article-title":"Lymphocyte-derived exosomal MicroRNAs promote pancreatic beta cell death and may contribute to type 1 diabetes development","volume":"29","author":"Guay","year":"2019","journal-title":"Cell Metab"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20235903","article-title":"Profiling of RNAs from human islet-derived exosomes in a model of type 1 diabetes","volume":"20","author":"Krishnan","year":"2019","journal-title":"Int J Mol Sci"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.822221","article-title":"Characterization of lncRNA profiles of plasma-derived exosomes from type 1 diabetes mellitus","volume":"13","author":"Pang","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B14","doi-asserted-by":"publisher","first-page":"5998","DOI":"10.1038\/s41598-017-05787-y","article-title":"Plasma-derived exosome characterization reveals a distinct microRNA signature in long duration type 1 diabetes","volume":"7","author":"Garcia-Contreras","year":"2017","journal-title":"Sci Rep"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bti430","article-title":"Automated genome annotation and pathway identification using the KEGG orthology (KO) as a controlled vocabulary","volume":"21","author":"Mao","year":"2005","journal-title":"Bioinformatics"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.756581","article-title":"The utility of exosomes in diagnosis and therapy of diabetes mellitus and associated complications","volume":"12","author":"Sun","year":"2021","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B17","doi-asserted-by":"publisher","first-page":"14470","DOI":"10.1038\/ncomms14470","article-title":"Malignant extracellular vesicles carrying MMP1 mRNA facilitate peritoneal dissemination in ovarian cancer","volume":"8","author":"Yokoi","year":"2017","journal-title":"Nat Commun"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.04.042","article-title":"In vivo imaging reveals extracellular vesicle-mediated phenocopying of metastatic behavior","volume":"161","author":"Zomer","year":"2015","journal-title":"Cell"},{"key":"B19","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.diabres.2018.03.044","article-title":"MicroRNA expression profile in plasma from type 1 diabetic patients: Case-control study and bioinformatic analysis","volume":"141","author":"Assmann","year":"2018","journal-title":"Diabetes Res Clin Pract"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-020-052","article-title":"Plasma circulating miR-23~27~24 clusters correlate with the immunometabolic derangement and predict c-peptide loss in children with type 1 diabetes","volume":"63","author":"Garavelli","year":"2020","journal-title":"Diabetologia"},{"key":"B21","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1007\/BF00505178","article-title":"Increasing incidence of diabetes mellitus in Norwegian children 0-14 years of age 1973-1982","volume":"32","author":"Joner","year":"1989","journal-title":"Diabetologia"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.21.7.1101","article-title":"Comparison of the seasonal pattern in the clinical onset of IDDM in Finland and Sardinia","volume":"21","author":"Karvonen","year":"1998","journal-title":"Diabetes Care"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.2181","article-title":"Infections in early life and development of type 1 diabetes","volume":"315","author":"Beyerlein","year":"2016","journal-title":"JAMA"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1001\/jamapediatrics.2013.158","article-title":"Respiratory infections in early life and the development of islet autoimmunity in children at increased type 1 diabetes risk: evidence from the BABYDIET study","volume":"167","author":"Beyerlein","year":"2013","journal-title":"JAMA Pediatr"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.83474-0","article-title":"An enterovirus strain isolated from diabetic child belongs to a genetic subcluster of echovirus 11, but is also neutralised with monotypic antisera to coxsackievirus A9","volume":"89","author":"Al-Hello","year":"2008","journal-title":"J Gen Virol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0700442104","article-title":"Coxsackie B4 virus infection of beta cells and natural killer cell insulitis in recent-onset type 1 diabetic patients","volume":"104","author":"Dotta","year":"2007","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197905243002102","article-title":"Isolation of a virus from the pancreas of a child with diabetic ketoacidosis","volume":"300","author":"Yoon","year":"1979","journal-title":"N Engl J Med"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.11.7325","article-title":"Murine gammaherpesvirus-68 infection alters self-antigen presentation and type 1 diabetes onset in NOD mice","volume":"179","author":"Smith","year":"2007","journal-title":"J Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.76.23.12097-12111.2002","article-title":"Toward testing the hypothesis that group b coxsackieviruses (CVB) trigger insulin-dependent diabetes: inoculating nonobese diabetic mice with CVB markedly lowers diabetes incidence","volume":"76","author":"Tracy","year":"2002","journal-title":"J Virol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.tem.2018.11.006","article-title":"BCG Therapy for type 1 diabetes: Restoration of balanced immunity and metabolism","volume":"30","author":"Kuhtreiber","year":"2019","journal-title":"Trends Endocrinol Metab"},{"key":"B31","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1038\/s41541-018-0062-8","article-title":"Long-term reduction in hyperglycemia in advanced type 1 diabetes: The value of induced aerobic glycolysis with BCG vaccinations","volume":"3","author":"Kuhtreiber","year":"2018","journal-title":"NPJ Vaccines"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1111\/joim.13050","article-title":"Benefits of BCG-induced metabolic switch from oxidative phosphorylation to aerobic glycolysis in autoimmune and nervous system diseases","volume":"288","author":"Faustman","year":"2020","journal-title":"J Intern Med"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2018.12.001","article-title":"Associations of mitochondrial and nuclear mitochondrial variants and genes with seven metabolic traits","volume":"104","author":"Kraja","year":"2019","journal-title":"Am J Hum Genet"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.2337\/db10-1241","article-title":"Mt-Nd2(a) modifies resistance against autoimmune type 1 diabetes in NOD mice at the level of the pancreatic beta-cell","volume":"60","author":"Chen","year":"2011","journal-title":"Diabetes"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.995610\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,13]],"date-time":"2022-09-13T05:19:02Z","timestamp":1663046342000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.995610\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,13]]},"references-count":34,"alternative-id":["10.3389\/fimmu.2022.995610"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.995610","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,13]]},"article-number":"995610"}}