{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T06:25:24Z","timestamp":1787034324858,"version":"build-2736575974"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"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>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Primary Sj\u00f6gren\u2019s syndrome (pSS) and type 1 diabetes mellitus (T1DM) share immune-inflammatory features, yet conserved pathogenic signatures linking these autoimmune disorders remain incompletely understood. The present research sought to uncover common molecular markers and dissect the underlying immune-metabolic cross-talk underlying pSS and T1DM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Gene expression profiles of patients with pSS and T1DM were retrieved from the Gene Expression Omnibus database, normalized, and corrected for batch effects prior to downstream analyses. Overlapping potential biomarkers were screened by integrating differential expression analysis, weighted gene co-expression network analysis and least absolute shrinkage and selection operator regression. Functional enrichment based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases was implemented to interpret gene biological properties, and a protein\u2013protein interaction network was further established afterwards. Diagnostic performance was evaluated using receiver operating characteristic analysis. Experimental validation was conducted in non-obese diabetic (NOD) mice using quantitative PCR, immunohistochemistry, and flow cytometry. The CIBERSORT algorithm was adopted to quantify immune cell infiltration levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>ZBTB16<\/jats:italic>\n                      was identified as a shared hub biomarker in both pSS and T1DM and exhibited favorable diagnostic performance. Experimental validation confirmed significantly reduced\n                      <jats:italic>ZBTB16<\/jats:italic>\n                      expression in peripheral blood mononuclear cells, salivary gland tissues, and pancreatic tissues of NOD mice. Gene Set Enrichment Analysis indicated that\n                      <jats:italic>ZBTB16<\/jats:italic>\n                      -associated signatures were enriched in mitochondrial-related processes, neuroactive ligand-receptor interactions, and ribosome-related pathways. Immune infiltration analysis revealed that resting natural killer (NK) cells were positively correlated with\n                      <jats:italic>ZBTB16<\/jats:italic>\n                      expression in both diseases. Flow cytometric analysis further confirmed a reduced proportion of resting NK cells in peripheral blood of NOD mice, consistent with the CIBERSORT-based prediction.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study identifies\n                      <jats:italic>ZBTB16<\/jats:italic>\n                      as a shared biomarker linking pSS and T1DM. Reduced resting NK-cell abundance was consistently observed in both computational and experimental analyses, and bioinformatic correlation analysis suggested a positive association with\n                      <jats:italic>ZBTB16<\/jats:italic>\n                      expression. These findings provide evidence for shared molecular and immunological signatures underlying the two autoimmune disorders and support further investigation of the biological role and diagnostic value of\n                      <jats:italic>ZBTB16<\/jats:italic>\n                      in pSS and T1DM.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1871048","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:37:39Z","timestamp":1787031459000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["ZBTB16-associated NK cell alterations reveal shared immunometabolic signatures linking primary Sj\u00f6gren\u2019s syndrome and type 1 diabetes mellitus"],"prefix":"10.3389","volume":"17","author":[{"given":"Mingzhe","family":"Xin","sequence":"first","affiliation":[{"name":"Department of Stomatology, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Mu","sequence":"additional","affiliation":[{"name":"Department of Orthodontics & Prosthodontics, The Second Affiliated Hospital, Zhejiang University School of Medicine","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Stomatology, The First Affiliated Hospital of Nanjing Medical University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haonan","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Stomatology, The First Affiliated Hospital of Nanjing Medical University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuwen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Stomatology, The First Affiliated Hospital of Nanjing Medical University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zelong","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shijia","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Orthodontics & Prosthodontics, The Second Affiliated Hospital, Zhejiang University School of Medicine","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University","place":["Nanjing, 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