{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:16:21Z","timestamp":1787026581114,"version":"build-2736575974"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"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>Cervical spondylosis (CS) is an age-related degenerative spinal disorder with increasing evidence linking its pathogenesis to immune aging. The genetic mechanisms connecting immune dysregulation to CS remain largely undefined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We integrated GWAS data from 484,598 individuals with single-cell eQTL profiles across 14 immune cell types, using Mendelian randomization (MR) and Bayesian colocalization to identify genes whose cell-type\u2013specific expression causally influences CS risk. Entropy analysis quantified lineage specificity of MR effects. Functional enrichment, drug\u2013gene interaction mapping, and protein\u2013protein interaction (PPI) network construction were used for target prioritization. Validation was performed using qPCR and ELISA in CS patient serum and 5-Aminosalicylic Acid (5-ASA) treatment in HUT78 T cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 118 genes exhibited suggestive or potential causal associations with CS, primarily enriched in CD4\n                      <jats:sup>+<\/jats:sup>\n                      and CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells. Five immune aging-related genes BMPR2, CHUK, CTNNB1, CTSB, and EZH2 emerged as central regulators based on entropy scores and colocalization evidence, PPI centrality, and druggability. These genes were validated in patient serum samples, showing age-associated expression changes and cytokine alterations. 5-ASA treatment modulated their expression and inflammatory cytokine levels\n                      <jats:italic>in vitro<\/jats:italic>\n                      , supporting its repurposing potential.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study reveals immune cell\u2013specific genetic regulators linking immune aging to cervical spondylosis and identifies 5-ASA as a candidate therapeutic agent. Our single-cell MR framework offers novel insights into immunogenetic mechanisms driving age-related spinal degeneration and highlights actionable targets for translational research.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1766215","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T05:32:49Z","timestamp":1771392769000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Identification of immune-mediated aging genes associated with cervical spondylosis through single-cell eQTL Mendelian 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