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Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Low back pain (LBP), primarily driven by intervertebral disc degeneration (IDD), imposes a significant global health burden. While type 2 diabetes mellitus (T2DM) is a recognized risk factor for IDD, the shared molecular mechanisms remain incompletely characterized.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study employed integrated bioinformatics (WGCNA, machine learning - LASSO, RF, ANN) on human T2DM and IDD transcriptomic datasets, alongside scRNA-seq analysis of diabetic mouse nucleus pulposus (NP) tissue, to identify key drivers of diabetes-associated IDD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Bioinformatics analysis of human data identified three diagnostic biomarkers (S100A12, IL1R1, FCGR2B) and constructed a robust ANN diagnostic model (AUCs: 0.744-0.868). IL1R1 emerged as the most significant risk factor. scRNA-seq revealed altered cellular composition in diabetic discs, notably increased proportion of granulocytes (predominantly neutrophils) and decreased proportion of nucleus pulposus (NP) cells. IL1R1 was highly expressed in specific diabetes-associated NP subpopulations and showed significant positive correlation with neutrophil infiltration. Functional enrichment linked IL1R1 to inflammation, DNA repair, and immune pathways. Furthermore, we constructed a regulatory network (STAT1\/STAT6-IL1R1-miRNAs-lncRNAs) and identified icariin as a potential therapeutic candidate via molecular docking.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>These findings establish IL1R1 as a pivotal molecular bridge connecting T2DM and IDD, driven by neutrophil-mediated inflammation and NP cell dysfunction, offering novel diagnostic and therapeutic avenues.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1692185","type":"journal-article","created":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T05:42:15Z","timestamp":1760506935000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Multi-omics analysis and evidence of IL1R1 as a potential biomarker for diabetes-associated intervertebral disc degeneration"],"prefix":"10.3389","volume":"16","author":[{"given":"Meng","family":"Yi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wancheng","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shijie","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jipeng","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukun","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixiang","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/S0140-6736(21)00733-9","article-title":"Low back pain","volume":"398","author":"Knezevic","year":"2021","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","first-page":"Itc113","DOI":"10.7326\/AITC202108170","article-title":"Low back pain","volume":"174","author":"Chou","year":"2021","journal-title":"Ann Intern Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)30970-9","article-title":"Non-specific low back pain","volume":"389","author":"Maher","year":"2017","journal-title":"Lancet"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.wneu.2021.09.066","article-title":"Fundamentals of intervertebral disc degeneration","volume":"157","author":"Kirnaz","year":"2022","journal-title":"World Neurosurg"},{"key":"B5","doi-asserted-by":"publisher","first-page":"101902","DOI":"10.1016\/j.arr.2023.101902","article-title":"Epigenetic modifications of inflammation in intervertebral disc degeneration","volume":"87","author":"Kang","year":"2023","journal-title":"Ageing Res Rev"},{"key":"B6","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1038\/s41584-021-00713-z","article-title":"A new immunometabolic perspective of intervertebral disc degeneration","volume":"18","author":"Francisco","year":"2022","journal-title":"Nat Rev Rheumatol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.spinee.2023.10.021","article-title":"Causal associations between modifiable risk factors and intervertebral disc degeneration","volume":"24","author":"Guo","year":"2024","journal-title":"Spine J"},{"key":"B8","doi-asserted-by":"publisher","first-page":"167635","DOI":"10.1016\/j.bbadis.2024.167635","article-title":"Meteorin-like protein alleviates intervertebral disc degeneration by suppressing lipid accumulation in nucleus pulposus cells via PPAR\u03b1-CPT1A activation","volume":"1871","author":"Huang","year":"2025","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"B9","doi-asserted-by":"publisher","first-page":"S20","DOI":"10.2337\/dc24-S002","article-title":"2. 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