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Metabolic reprogramming has emerged as a critical regulator of T cell function, yet the roles of specific cholesterol\u2010associated proteins during T cell fate trajectories remain unclear. Here, using an in\u00a0vivo CRISPR screen in CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells during infection with a customized sgRNA library targeting key cholesterol metabolism\u2010associated proteins, we successfully identified several candidate targets, including the LBR (Lamin B Receptor).\n                    <jats:italic>Lbr<\/jats:italic>\n                    knockout significantly reduced the proportion and absolute number of short\u2010lived effector cells (SLECs), severely impairing effector responses, while concomitantly increasing the memory precursor population upon LCMV infection. Furthermore, transcriptomic analysis revealed that\n                    <jats:italic>Lbr<\/jats:italic>\n                    depletion markedly altered signaling pathways governing effector T cell differentiation. These findings reveal the role of LBR in modulating effector and memory T cell differentiation, suggesting it as a potential target for metabolic reprogramming to enhance T cell\u2010based immunotherapies.\n                  <\/jats:p>","DOI":"10.1096\/fj.202602909r","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T07:15:51Z","timestamp":1790666151000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["In vivo\n                    <scp>CRISPR<\/scp>\n                    Screening Reveals\n                    <scp>LBR<\/scp>\n                    as a Regulator of\n                    <scp>CD8<\/scp>\n                    <sup>+<\/sup>\n                    T Cell Fate Decision"],"prefix":"10.1096","volume":"40","author":[{"given":"Qiying","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Immune Response and Immunotherapy, Department of Oncology, the First Affiliated Hospital of USTC, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, School of Basic Medical Sciences University of Science and Technology of China  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuya","family":"Chang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Immune Response and Immunotherapy, Department of Oncology, the First Affiliated Hospital of USTC, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, School of Basic Medical Sciences University of Science and Technology of China  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengli","family":"Zhao","sequence":"additional","affiliation":[{"name":"Shanghai Engineering Research Center of Organ Repair, School of Life Sciences Shanghai University  Shanghai 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