In vivo CRISPR Screening Reveals LBR as a Regulator of CD8⁺ T Cell Fate Decision.

Authors

Qiying Zhang, Shuya Chang, Shengli Zhao, Weixin Zhang, Rong Wang, Mingyang Zhong, Guanfeng Liu, Xiaojing Li, Ao Guo

Published in

FASEB journal : official publication of the Federation of American Societies for Experimental Biology. Volume 40. Issue 19. Pages e72318. Oct 15, 2026.

Abstract

CD8⁺ T cells play an important role in anti-infection and anti-tumor immunity. Metabolic reprogramming has emerged as a critical regulator of T cell function, yet the roles of specific cholesterol-associated proteins during T cell fate trajectories remain unclear. Here, using an in vivo CRISPR screen in CD8⁺ T cells during infection with a customized sgRNA library targeting key cholesterol metabolism-associated proteins, we successfully identified several candidate targets, including the LBR (Lamin B Receptor). Lbr knockout significantly reduced the proportion and absolute number of short-lived effector cells (SLECs), severely impairing effector responses, while concomitantly increasing the memory precursor population upon LCMV infection. Furthermore, transcriptomic analysis revealed that Lbr 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-based immunotherapies.

PMID:
42806792
Bibliographic data and abstract were imported from PubMed on 29 Sep 2026.

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