{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T11:59:27Z","timestamp":1777982367661,"version":"3.51.4"},"reference-count":51,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Immune ageing impairs adaptive and innate responses, yet the spleen remains underexplored by cross\u2010cohort single\u2010cell studies. We profiled splenocytes from young, old and chronically stressed old mice with natural microbiota using single\u2010cell RNA sequencing. Ageing was characterised by reduced lymphocyte competence and elevated stress responses. Within\n                    <jats:italic>Gzmk<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, young mice were enriched for Gzmk\u2010high cells, whereas in old mice, both Gzmk\u2010high and Gzmk\u2010low cells showed greater heterogeneity and functional alterations: exhaustion in Gzmk\u2010high and inflammation in Gzmk\u2010low cells. Natural killer (NK) cells and macrophages exhibited reduced cytotoxic potential and sustained pro\u2010inflammatory polarisation, respectively. Chronic stress caused modest compositional shifts that partially counteracted age\u2010related changes. Furthermore, we integrated our dataset with six published datasets to build a comprehensive atlas with &gt; 272,000 splenocytes. Atlas\u2010level annotation showed reproducible compositional shifts across datasets. Conserved ageing signatures included loss of NK effector genes (\n                    <jats:italic>Zeb2, Prf1<\/jats:italic>\n                    ), decline of na\u00efve T quiescence (\n                    <jats:italic>Lef1, Il7r<\/jats:italic>\n                    ) with stress induction (\n                    <jats:italic>Rbm3, Socs3<\/jats:italic>\n                    ), gain of survival\/pro\u2010inflammatory\/exhaustion genes (\n                    <jats:italic>Bcl2, S100a6, Ccl5, Lag3<\/jats:italic>\n                    ) in effector T cells, and altered differentiation and regulation (\n                    <jats:italic>Zbtb32, Zbtb20, Zfp318, Ighd, Cr2<\/jats:italic>\n                    ) in B cells. Our results define conserved features of splenic immunosenescence and provide an atlas for dissecting splenic immune alterations.\n                  <\/jats:p>","DOI":"10.1002\/eji.70170","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T13:48:25Z","timestamp":1773323305000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Single\u2010Cell Profiling of Splenic Immune Ageing and Chronic Stress Adaptations in Mice With Natural Microbiota"],"prefix":"10.1002","volume":"56","author":[{"given":"Chinna Susan","family":"Philip","sequence":"first","affiliation":[{"name":"Molecular Pathology Research Group, Institute of Biomedicine and Translational Medicine University of Tartu  Tartu 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