In Vivo CRISPR Screening Reveals CHD7 as a Positive Regulator of Short-lived Effector Cells
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.
Authors
- Ivy S. L. Streeter (ORCID: https://orcid.org/0000-0003-0729-1042)
- Dillon G. Patterson (ORCID: https://orcid.org/0000-0001-6053-5216)
- Thao H. Nguyen (ORCID: https://orcid.org/0000-0002-2767-0528)
- Jacob E. Gillis (ORCID: https://orcid.org/0000-0001-6248-693X)
- Arlene H. Sharpe (ORCID: https://orcid.org/0000-0002-9736-2109)
- Nir Hacohen (ORCID: https://orcid.org/0000-0002-2349-2656)
- John G. Doench (ORCID: https://orcid.org/0000-0002-3707-9889)
- Jossef F. Osborn (ORCID: https://orcid.org/0000-0002-3867-8509)
- Matthew Coxe (ORCID: https://orcid.org/0000-0002-8791-7094)
- Martin W. LaFleur (ORCID: https://orcid.org/0000-0002-5017-774X)
- Marc A. Schwartz (ORCID: https://orcid.org/0000-0003-3869-0150)
- Jasmin M. D’Andrea
- Lauren E. Milling (ORCID: https://orcid.org/0009-0002-4604-9435)
- Qin Tjokrosurjo
Institutions
- Broad Institute (US)
- Brigham and Women's Hospital (US)
- Boston Children's Hospital (US)
- Boston Biomedical Research Institute (US)
- Harvard University (US)
- Massachusetts General Hospital (US)
- Boston VA Research Institute (US)
- Boston Children's Museum (US)
Publication Details
- Journal
- The Journal of Immunology
- Published
- 2024-10-07
- DOI
- https://doi.org/10.4049/jimmunol.2400213
- Primary Topic
- Immune responses and vaccinations
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Cancer Research Institute
- Massachusetts General Hospital
- Dana-Farber Cancer Institute
- Broad Institute
- National Cancer Institute
- National Institute of Allergy and Infectious Diseases