First Author | LaFleur MW | Year | 2024 |
Journal | J Immunol | Volume | 213 |
Issue | 10 | Pages | 1528-1541 |
PubMed ID | 39373572 | Mgi Jnum | J:360933 |
Mgi Id | MGI:7787373 | Doi | 10.4049/jimmunol.2400213 |
Citation | LaFleur MW, et al. (2024) In Vivo CRISPR Screening Reveals CHD7 as a Positive Regulator of Short-lived Effector Cells. J Immunol 213(10):1528-1541 |
abstractText | CD8+ T cells differentiate into two subpopulations in response to acute viral infection: memory precursor effector cells (MPECs) and short-lived effector cells (SLECs). MPECs and SLECs are epigenetically distinct; however, the epigenetic regulators required for formation of these subpopulations are mostly unknown. In this study, we performed an in vivo CRISPR screen in murine naive CD8+ T cells to identify the epigenetic regulators required for MPEC and SLEC formation, using the acute lymphocytic choriomeningitis virus Armstrong infection model. We identified the ATP-dependent chromatin remodeler CHD7 (chromodomain-helicase DNA-binding protein 7) as a positive regulator of SLEC formation, as knockout (KO) of Chd7 reduced SLECs numerically. In contrast, KO of Chd7 increased the formation of central memory T cells following pathogen clearance yet attenuated memory cell expansion following a rechallenge. These findings establish CHD7 as a novel positive regulator of SLEC and a negative regulator of central memory T cell formation. |