{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T23:52:49Z","timestamp":1789084369886,"version":"build-2803163510"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T00:00:00Z","timestamp":1762819200000},"content-version":"vor","delay-in-days":314,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82160596"],"award-info":[{"award-number":["82160596"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Mediators of Inflammation"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Systemic lupus erythematosus (SLE) is a complex autoimmune disorder marked by immune dysregulation and multiorgan involvement. This study investigates the role of the ubiquitination\u2010related gene EEF1A1 in SLE pathogenesis, focusing on T cell dysfunction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Single\u2010cell RNA sequencing (scRNA\u2010seq) data from the GSE135779 dataset was analyzed to characterize the cellular composition of SLE samples. Clustering analysis identified 15 T cell subpopulations, with seven clusters notably depleted in SLE. Trajectory analysis indicated progressive transcriptional dysregulation during T cell differentiation. High\u2010dimensional weighted gene coexpression network analysis (hdWGCNA) and LASSO regression highlighted EEF1A1 as a key ubiquitination\u2010related hub gene. EEF1A1 expression was significantly elevated in SLE T cells, while its ubiquitinated form was reduced, suggesting impaired proteasomal degradation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Functional assays demonstrated that EEF1A1 overexpression enhances STAT1 phosphorylation (p\u2010STAT1) without altering total STAT1 protein levels, leading to T cell dysfunction. In vitro and in vivo experiments revealed that EEF1A1 overexpression skews the T helper 1 (Th1)\/T helper 2 (Th2) balance towards a Th1\u2010dominant phenotype. In MRL\/lpr mouse models, EEF1A1 overexpression exacerbated renal pathology, including increased proteinuria and immune complex deposition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings suggest that EEF1A1 contributes to SLE pathogenesis by promoting STAT1\u2010mediated T cell dysfunction and Th1\/Th2 imbalance. EEF1A1 emerges as a potential biomarker and therapeutic target, offering new insights into the post\u2010translational regulatory mechanisms underlying SLE.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/mi\/3708640","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T08:13:58Z","timestamp":1762848838000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Single\u2010Cell Transcriptomics Uncover EEF1A1\u2010Driven Ubiquitination Dysregulation in T Cell Exhaustion and SLE Pathogenesis via STAT1\u2010Mediated Th1\/Th2 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