{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T06:39:27Z","timestamp":1790145567291,"version":"4.0.1"},"reference-count":55,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sig Transduct Target Ther"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Type 1 diabetes (T1D) exhibits age-related heterogeneity in clinical progression and immune pathology, yet the underlying molecular mechanisms remain poorly understood. Here, we integrate microbiome, metabolome, lipidome, and transcriptome profiling from 108 newly diagnosed pediatric patients with T1D, along with 56 healthy controls, to investigate age-related endotypes. Patients were stratified into early-onset (E-T1D, &lt;7 years), intermediate-onset (I-T1D, 7-12 years), and late-onset (L-T1D, \u226513 years) groups. Multi-omics analyses revealed distinct molecular signatures among T1D subgroups. The most enriched microbial signatures were the genus\n                    <jats:italic>Acetatifactor<\/jats:italic>\n                    in E-T1D, the phylum\n                    <jats:italic>Firmicutes A<\/jats:italic>\n                    in I-T1D, and the family\n                    <jats:italic>Bacteroidaceae<\/jats:italic>\n                    in L-T1D (Linear Discriminant Analysis scores = 3.49, 5.56, and 5.78, respectively). For metabolites, pipecolic acid increased most in E-T1D, testosterone in I-T1D, while N-acetylhomocitrulline was most enriched in L-T1D. Lipidomic profiling revealed subgroup-specific alterations, with increased levels of LPA(16:1) in E-T1D, TG(16:0\/18:2\/18:3) in I-T1D, and TG(18:0\/18:1\/18:1) in L-T1D. The proportion of peripheral B cells to total lymphocytes was the highest in E-T1D (median = 11.64%) and associated with upregulated immune-related pathways, lowest in L-T1D (median = 5.99%) and linked to metabolic processes, while I-T1D (median = 8.47%) exhibited intermediate features of both groups. Integration of multi-omics interaction networks and experimental validation revealed that the microbial species\n                    <jats:italic>Dialister invisus<\/jats:italic>\n                    may promote peripheral B cell proliferation via docosapentaenoic acid, potentially contributing to early-onset T1D. Together, these findings provide a molecular framework for understanding age-related T1D endotypes and suggest potential targets for precision intervention.\n                  <\/jats:p>","DOI":"10.1038\/s41392-026-02724-2","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T09:52:39Z","timestamp":1781517159000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Multi-omics reveals microbiota, metabolite, and immunological heterogeneity of age-related endotypes in type 1 diabetes"],"prefix":"10.1038","volume":"11","author":[{"given":"Lanxin","family":"Pan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiling","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Yue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1617-2125","authenticated-orcid":false,"given":"Yu","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaohe","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xulin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoya","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiru","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuang","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8395-9476","authenticated-orcid":false,"given":"Xueying","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7889-1697","authenticated-orcid":false,"given":"Jianping","family":"Weng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,15]]},"reference":[{"key":"2724_CR1","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1038\/s41574-019-0254-y","volume":"15","author":"J Ilonen","year":"2019","unstructured":"Ilonen, J., Lempainen, J. & Veijola, R. The heterogeneous pathogenesis of type 1 diabetes mellitus. Nat. Rev. Endocrinol. 15, 635\u2013650 (2019).","journal-title":"Nat. Rev. Endocrinol."},{"key":"2724_CR2","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1038\/s41392-024-01952-8","volume":"9","author":"Y Song","year":"2024","unstructured":"Song, Y., Li, J. & Wu, Y. Evolving understanding of autoimmune mechanisms and new therapeutic strategies of autoimmune disorders. Signal Transduct. Target Ther. 9, 263 (2024).","journal-title":"Signal Transduct. Target Ther."},{"key":"2724_CR3","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.16","volume":"3","author":"A Katsarou","year":"2017","unstructured":"Katsarou, A. et al. Type 1 diabetes mellitus. Nat. Rev. Dis. Prim. 3, 17016 (2017).","journal-title":"Nat. Rev. Dis. Prim."},{"key":"2724_CR4","doi-asserted-by":"publisher","first-page":"j5295","DOI":"10.1136\/bmj.j5295","volume":"360","author":"J Weng","year":"2018","unstructured":"Weng, J. et al. Incidence of type 1 diabetes in China, 2010-13: population based study. BMJ 360, j5295 (2018).","journal-title":"BMJ"},{"key":"2724_CR5","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1016\/S2213-8587(22)00218-2","volume":"10","author":"GA Gregory","year":"2022","unstructured":"Gregory, G. A. et al. Global incidence, prevalence, and mortality of type 1 diabetes in 2021 with projection to 2040: a modelling study. Lancet Diab. Endocrinol. 10, 741\u2013760 (2022).","journal-title":"Lancet Diab. Endocrinol."},{"key":"2724_CR6","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1038\/s41574-023-00853-0","volume":"19","author":"MJ Redondo","year":"2023","unstructured":"Redondo, M. J. & Morgan, N. G. Heterogeneity and endotypes in type 1 diabetes mellitus. Nat. Rev. Endocrinol. 19, 542\u2013554 (2023).","journal-title":"Nat. Rev. Endocrinol."},{"key":"2724_CR7","doi-asserted-by":"publisher","first-page":"5","DOI":"10.2337\/dc19-0880","volume":"43","author":"M Battaglia","year":"2020","unstructured":"Battaglia, M. et al. Introducing the endotype concept to address the challenge of disease heterogeneity in type 1 diabetes. Diab. Care 43, 5\u201312 (2020).","journal-title":"Diab. Care"},{"key":"2724_CR8","doi-asserted-by":"publisher","first-page":"3835","DOI":"10.2337\/db14-0365","volume":"63","author":"S Arif","year":"2014","unstructured":"Arif, S. et al. Blood and islet phenotypes indicate immunological heterogeneity in type 1 diabetes. Diabetes 63, 3835\u20133845 (2014).","journal-title":"Diabetes"},{"key":"2724_CR9","doi-asserted-by":"publisher","first-page":"1362","DOI":"10.2337\/db15-1615","volume":"65","author":"P Leete","year":"2016","unstructured":"Leete, P. et al. Differential insulitic profiles determine the extent of \u03b2-cell destruction and the age at onset of type 1 diabetes. Diabetes 65, 1362\u20131369 (2016).","journal-title":"Diabetes"},{"key":"2724_CR10","doi-asserted-by":"publisher","first-page":"1258","DOI":"10.1007\/s00125-020-05115-6","volume":"63","author":"P Leete","year":"2020","unstructured":"Leete, P. et al. Studies of insulin and proinsulin in pancreas and serum support the existence of aetiopathological endotypes of type 1 diabetes associated with age at diagnosis. Diabetologia 63, 1258\u20131267 (2020).","journal-title":"Diabetologia"},{"key":"2724_CR11","doi-asserted-by":"publisher","first-page":"871","DOI":"10.2337\/dc21-1251","volume":"45","author":"A Parviainen","year":"2022","unstructured":"Parviainen, A. et al. Heterogeneity of type 1 diabetes at diagnosis supports existence of age-related endotypes. Diab. Care 45, 871\u2013879 (2022).","journal-title":"Diab. Care"},{"key":"2724_CR12","doi-asserted-by":"publisher","first-page":"169","DOI":"10.2337\/dc19-0803","volume":"43","author":"JRJ Inshaw","year":"2020","unstructured":"Inshaw, J. R. J., Cutler, A. J., Crouch, D. J. M., Wicker, L. S. & Todd, J. A. Genetic variants predisposing most strongly to type 1 diabetes diagnosed under age 7 years lie near candidate genes that function in the immune system and in pancreatic \u03b2-cells. Diab. Care 43, 169\u2013177 (2020).","journal-title":"Diab. Care"},{"key":"2724_CR13","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1016\/S0140-6736(18)31506-X","volume":"392","author":"A Rawshani","year":"2018","unstructured":"Rawshani, A. et al. Excess mortality and cardiovascular disease in young adults with type 1 diabetes in relation to age at onset: a nationwide, register-based cohort study. Lancet 392, 477\u2013486 (2018).","journal-title":"Lancet"},{"key":"2724_CR14","doi-asserted-by":"publisher","first-page":"2438","DOI":"10.1038\/s41591-023-02502-5","volume":"29","author":"DK Tobias","year":"2023","unstructured":"Tobias, D. K. et al. Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine. Nat. Med. 29, 2438\u20132457 (2023).","journal-title":"Nat. Med."},{"key":"2724_CR15","doi-asserted-by":"crossref","unstructured":"Powers, A. C. Type 1 diabetes mellitus: much progress, many opportunities. J. Clin. Invest. 131, e142242 (2021).","DOI":"10.1172\/JCI142242"},{"key":"2724_CR16","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1146\/annurev-med-050219-034524","volume":"72","author":"A Balasubramanyam","year":"2021","unstructured":"Balasubramanyam, A. Defining and classifying new subgroups of diabetes. Annu. Rev. Med. 72, 63\u201374 (2021).","journal-title":"Annu. Rev. Med."},{"key":"2724_CR17","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1152\/physrev.00003.2010","volume":"91","author":"TL van Belle","year":"2011","unstructured":"van Belle, T. L., Coppieters, K. T. & von Herrath, M. G. Type 1 diabetes: etiology, immunology, and therapeutic strategies. Physiol. Rev. 91, 79\u2013118 (2011).","journal-title":"Physiol. Rev."},{"key":"2724_CR18","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1038\/s41586-018-0620-2","volume":"562","author":"T Vatanen","year":"2018","unstructured":"Vatanen, T. et al. The human gut microbiome in early-onset type 1 diabetes from the TEDDY study. Nature 562, 589 (2018).","journal-title":"Nature"},{"key":"2724_CR19","doi-asserted-by":"crossref","unstructured":"Mokhtari, P., Jambal, P., Metos, J. M., Shankar, K. & Babu, P. V. A. Microbial taxonomic and functional shifts in adolescents with type 1 diabetes are associated with clinical and dietary factors. Ebiomedicine 93, 104641 (2023).","DOI":"10.1016\/j.ebiom.2023.104641"},{"key":"2724_CR20","doi-asserted-by":"publisher","first-page":"2975","DOI":"10.1084\/jem.20081800","volume":"205","author":"M Oresic","year":"2008","unstructured":"Oresic, M. et al. Dysregulation of lipid and amino acid metabolism precedes islet autoimmunity in children who later progress to type 1 diabetes. J. Exp. Med. 205, 2975\u20132984 (2008).","journal-title":"J. Exp. Med."},{"key":"2724_CR21","doi-asserted-by":"crossref","unstructured":"Yuan, X. X. et al. Functional and metabolic alterations of gut microbiota in children with new-onset type 1 diabetes. Nat. Commun. 13, 6356 (2022).","DOI":"10.1038\/s41467-022-33656-4"},{"key":"2724_CR22","doi-asserted-by":"crossref","unstructured":"Honardoost, M. A. et al. Systematic immune cell dysregulation and molecular subtypes revealed by single-cell RNA-seq of subjects with type 1 diabetes. Genome Med. 16, 45 (2024).","DOI":"10.1186\/s13073-024-01300-z"},{"key":"2724_CR23","doi-asserted-by":"crossref","unstructured":"Cuijpers, S. A. G. et al. Chromokinesin KIF4A teams up with stathmin 1 to regulate abscission in a SUMO-dependent manner. J Cell Sci. 133, jcs248591 (2020).","DOI":"10.1242\/jcs.248591"},{"key":"2724_CR24","doi-asserted-by":"publisher","first-page":"110775","DOI":"10.1016\/j.cellsig.2023.110775","volume":"109","author":"R Liu","year":"2023","unstructured":"Liu, R. et al. STNM1 in human cancers: role, function and potential therapy sensitizer. Cell Signal 109, 110775 (2023).","journal-title":"Cell Signal"},{"key":"2724_CR25","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1007\/s13238-020-00814-7","volume":"12","author":"J Wu","year":"2021","unstructured":"Wu, J., Wang, K., Wang, X., Pang, Y. & Jiang, C. The role of the gut microbiome and its metabolites in metabolic diseases. Protein Cell 12, 360\u2013373 (2021).","journal-title":"Protein Cell"},{"key":"2724_CR26","doi-asserted-by":"crossref","unstructured":"Kolli, U. et al. Multi-omics analysis revealing the interplay between gut microbiome and the host following opioid use. Gut Microbes 15, 2246184 (2023).","DOI":"10.1080\/19490976.2023.2246184"},{"key":"2724_CR27","doi-asserted-by":"crossref","unstructured":"Qian, X. H. et al. Multi-omics data reveals aberrant gut microbiota-host glycerophospholipid metabolism in association with neuroinflammation in APP\/PS1 mice. Gut Microbes 15, 2282790 (2023).","DOI":"10.1080\/19490976.2023.2282790"},{"key":"2724_CR28","doi-asserted-by":"crossref","unstructured":"Shen, Y. et al. Alterations in gut microbiome and metabolomics in chronic hepatitis B infection-associated liver disease and their impact on peripheral immune response. Gut Microbes 15, 2155018 (2023).","DOI":"10.1080\/19490976.2022.2155018"},{"key":"2724_CR29","doi-asserted-by":"crossref","unstructured":"Zhao, Q. et al. Intestinal dysbiosis exacerbates the pathogenesis of psoriasis-like phenotype through changes in fatty acid metabolism. Signal Transduct Target Ther. 8, 40 (2023).","DOI":"10.1038\/s41392-022-01219-0"},{"key":"2724_CR30","doi-asserted-by":"publisher","first-page":"416","DOI":"10.2337\/dc08-1775","volume":"32","author":"J Guy","year":"2009","unstructured":"Guy, J. et al. Lipid and lipoprotein profiles in youth with and without type 1 diabetes The SEARCH for diabetes in youth case-control study. Diab. Care 32, 416\u2013420 (2009).","journal-title":"Diab. Care"},{"key":"2724_CR31","first-page":"1277","volume":"102","author":"B Jonsdottir","year":"2017","unstructured":"Jonsdottir, B. et al. Thyroid and islet autoantibodies predict autoimmune thyroid disease at type 1 diabetes diagnosis. J. Clin. Endocr. Metab. 102, 1277\u20131285 (2017).","journal-title":"J. Clin. Endocr. Metab."},{"key":"2724_CR32","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.ijbiomac.2022.01.152","volume":"204","author":"Y Wu","year":"2022","unstructured":"Wu, Y. et al. Preventive effects of polysaccharides from Physalis alkekengi L. on dietary advanced glycation end product-induced insulin resistance in mice associated with the modulation of gut microbiota. Int J. Biol. Macromol. 204, 204\u2013214 (2022).","journal-title":"Int J. Biol. Macromol."},{"key":"2724_CR33","doi-asserted-by":"crossref","unstructured":"Ge, X. D. et al. Porous starch microspheres loaded with luteolin exhibit hypoglycemic activities and alter gut microbial communities in type 2 diabetes mellitus mice. Food Funct. 16, 54-70 (2025).","DOI":"10.1039\/D4FO02907K"},{"key":"2724_CR34","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1681\/ASN.2016020231","volume":"28","author":"N Sandholm","year":"2017","unstructured":"Sandholm, N. et al. The genetic landscape of renal complications in type 1 diabetes. J. Am. Soc. Nephrol. 28, 557\u2013574 (2017).","journal-title":"J. Am. Soc. Nephrol."},{"key":"2724_CR35","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1111\/pedi.12524","volume":"19","author":"A Galderisi","year":"2018","unstructured":"Galderisi, A. et al. Metabolomics reveals new metabolic perturbations in children with type 1 diabetes. Pediatr. Diab. 19, 59\u201367 (2018).","journal-title":"Pediatr. Diab."},{"key":"2724_CR36","doi-asserted-by":"crossref","unstructured":"Taiwo, A. et al. Metabolite perturbations in type 1 diabetes associated with metabolic dysfunction-associated steatotic liver disease. Front Endocrinol. 16, 1500242 (2025).","DOI":"10.3389\/fendo.2025.1500242"},{"key":"2724_CR37","doi-asserted-by":"crossref","unstructured":"Ye, L. et al. Aflatoxin B1-induced liver pyroptosis is mediated by disturbing the gut microbial metabolites: the roles of pipecolic acid and norepinephrine. J. Hazard Mater. 474, 134822 (2024).","DOI":"10.1016\/j.jhazmat.2024.134822"},{"key":"2724_CR38","doi-asserted-by":"publisher","first-page":"17915","DOI":"10.1007\/s11356-018-1997-z","volume":"25","author":"C Castro-Correia","year":"2018","unstructured":"Castro-Correia, C. et al. Phthalates and type 1 diabetes: is there any link? Environ. Sci. Pollut. R. 25, 17915\u201317919 (2018).","journal-title":"Environ. Sci. Pollut. R."},{"key":"2724_CR39","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1128\/MMBR.00032-06","volume":"71","author":"Y Xu","year":"2007","unstructured":"Xu, Y., Labedan, B. & Glansdorff, N. Surprising arginine biosynthesis: a reappraisal of the enzymology and evolution of the pathway in microorganisms. Microbiol. Mol. Biol. Rev. 71, 36\u201347 (2007).","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"2724_CR40","doi-asserted-by":"crossref","unstructured":"Abo El-Magd, N. F., Ramadan, N. M. & Eraky, S. M. The ameliorative effect of bromelain on STZ-induced type 1 diabetes in rats through Oxi-LDL\/LPA\/LPAR1 pathway. Life Sci. 285, 119982 (2021).","DOI":"10.1016\/j.lfs.2021.119982"},{"key":"2724_CR41","doi-asserted-by":"crossref","unstructured":"Barranco-Altirriba, M. et al. Lipidome characterisation and sex-specific differences in type 1 and type 2 diabetes mellitus. Cardiovasc. Diabetol. 23, 109 (2024).","DOI":"10.1186\/s12933-024-02202-5"},{"key":"2724_CR42","doi-asserted-by":"publisher","first-page":"1483","DOI":"10.2337\/db23-0353","volume":"72","author":"M Sch\u00f6n","year":"2023","unstructured":"Sch\u00f6n, M. et al. Intramyocellular triglyceride content during the early course of type 1 and type 2 diabetes. Diabetes 72, 1483\u20131492 (2023).","journal-title":"Diabetes"},{"key":"2724_CR43","doi-asserted-by":"crossref","unstructured":"Luo, S. W. et al. TCL1A in na\u00efve B cells as a therapeutic target for type 1 diabetes. Ebiomedicine 113, 105593 (2025).","DOI":"10.1016\/j.ebiom.2025.105593"},{"key":"2724_CR44","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1038\/s41577-023-00985-4","volume":"24","author":"KC Herold","year":"2024","unstructured":"Herold, K. C. et al. The immunology of type 1 diabetes. Nat. Rev. Immunol. 24, 435\u2013451 (2024).","journal-title":"Nat. Rev. Immunol."},{"key":"2724_CR45","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1126\/science.abh1654","volume":"373","author":"JA Bluestone","year":"2021","unstructured":"Bluestone, J. A., Buckner, J. H. & Herold, K. C. Immunotherapy: building a bridge to a cure for type 1 diabetes. Science 373, 510\u2013515 (2021).","journal-title":"Science"},{"key":"2724_CR46","doi-asserted-by":"publisher","first-page":"700","DOI":"10.1002\/dmrr.2790","volume":"32","author":"C Maffeis","year":"2016","unstructured":"Maffeis, C. et al. Association between intestinal permeability and faecal microbiota composition in Italian children with beta cell autoimmunity at risk for type 1 diabetes. Diab. Metab. Res. Rev. 32, 700\u2013709 (2016).","journal-title":"Diab. Metab. Res. Rev."},{"key":"2724_CR47","doi-asserted-by":"publisher","first-page":"2539","DOI":"10.1007\/s00125-024-06237-x","volume":"67","author":"S Masalin","year":"2024","unstructured":"Masalin, S. et al. Analysis of early-pregnancy metabolome in early- and late-onset gestational diabetes reveals distinct associations with maternal overweight. Diabetologia 67, 2539\u20132554 (2024).","journal-title":"Diabetologia"},{"key":"2724_CR48","doi-asserted-by":"crossref","unstructured":"Li, J. et al. Serum IL-17A concentration and a IL17RA single nucleotide polymorphism contribute to the risk of autoimmune type 1 diabetes. Diabetes Metab. Res. Rev. 38, e3547 (2022).","DOI":"10.1002\/dmrr.3547"},{"key":"2724_CR49","doi-asserted-by":"publisher","first-page":"356ra119","DOI":"10.1126\/scitranslmed.aad9943","volume":"8","author":"C Hundhausen","year":"2016","unstructured":"Hundhausen, C. et al. Enhanced T cell responses to IL-6 in type 1 diabetes are associated with early clinical disease and increased IL-6 receptor expression. Sci. Transl. Med. 8, 356ra119 (2016).","journal-title":"Sci. Transl. Med."},{"key":"2724_CR50","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1111\/j.1365-2184.2007.00429.x","volume":"40","author":"SY Baik","year":"2007","unstructured":"Baik, S. Y. et al. Identification of stathmin 1 expression induced by Epstein-Barr virus in human B lymphocytes. Cell Proliferat 40, 268\u2013281 (2007).","journal-title":"Cell Proliferat"},{"key":"2724_CR51","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1002\/dmrr.337","volume":"19","author":"HS Jun","year":"2003","unstructured":"Jun, H. S. & Yoon, J. W. A new look at viruses in type 1 diabetes. Diab. Metab. Res. Rev. 19, 8\u201331 (2003).","journal-title":"Diab. Metab. Res. Rev."},{"key":"2724_CR52","doi-asserted-by":"publisher","DOI":"10.1126\/science.abf1970","volume":"376","author":"RK Perez","year":"2022","unstructured":"Perez, R. K. et al. Single-cell RNA-seq reveals cell type-specific molecular and genetic associations to lupus. Science 376, eabf1970 (2022).","journal-title":"Science"},{"key":"2724_CR53","doi-asserted-by":"publisher","first-page":"2836","DOI":"10.1016\/j.immuni.2023.10.013","volume":"56","author":"M Terekhova","year":"2023","unstructured":"Terekhova, M. et al. Single-cell atlas of healthy human blood unveils age-related loss of NKG2C(+)GZMB(-)CD8(+) memory T cells and accumulation of type 2 memory T cells. Immunity 56, 2836\u20132854 e2839 (2023).","journal-title":"Immunity"},{"key":"2724_CR54","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09234-6","volume":"10","author":"Y Zhou","year":"2019","unstructured":"Zhou, Y. et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat. Commun. 10, 1523 (2019).","journal-title":"Nat. Commun."},{"key":"2724_CR55","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1093\/nar\/30.1.207","volume":"30","author":"R Edgar","year":"2002","unstructured":"Edgar, R., Domrachev, M. & Lash, A. E. Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res. 30, 207\u2013210 (2002).","journal-title":"Nucleic Acids Res."}],"container-title":["Signal Transduction and Targeted Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41392-026-02724-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41392-026-02724-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41392-026-02724-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T09:52:50Z","timestamp":1781517170000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41392-026-02724-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,15]]},"references-count":55,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["2724"],"URL":"https:\/\/doi.org\/10.1038\/s41392-026-02724-2","relation":{},"ISSN":["2059-3635"],"issn-type":[{"value":"2059-3635","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,15]]},"assertion":[{"value":"4 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 January 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 March 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 June 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"233"}}