Dependence on Bcl6 and Blimp1 drive distinct differentiation of murine memory and follicular helper CD4+ T cells.

Autor:	Ciucci T; Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.; David H. Smith Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY., Vacchio MS; Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD., Chen T; Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD., Nie J; Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD., Chopp LB; Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.; Immunology Graduate Group, University of Pennsylvania Medical School, Philadelphia, PA., McGavern DB; Viral Immunology and Intravital Imaging Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD., Kelly MC; Single Cell Analysis Facility, Cancer Research Technology Program, Frederick National Laboratory, Bethesda, MD., Bosselut R; Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Jazyk:	angličtina
Zdroj:	The Journal of experimental medicine [J Exp Med] 2022 Jan 03; Vol. 219 (1). Date of Electronic Publication: 2021 Nov 18.
DOI:	10.1084/jem.20202343
Abstrakt:	During the immune response, CD4+ T cells differentiate into distinct effector subtypes, including follicular helper T (Tfh) cells that help B cells, and into memory cells. Tfh and memory cells are required for long-term immunity; both depend on the transcription factor Bcl6, raising the question whether they differentiate through similar mechanisms. Here, using single-cell RNA and ATAC sequencing, we show that virus-responding CD4+ T cells lacking both Bcl6 and Blimp1 can differentiate into cells with transcriptomic, chromatin accessibility, and functional attributes of memory cells but not of Tfh cells. Thus, Bcl6 promotes memory cell differentiation primarily through its repression of Blimp1. These findings demonstrate that distinct mechanisms underpin the differentiation of memory and Tfh CD4+ cells and define the Bcl6-Blimp1 axis as a potential target for promoting long-term memory T cell differentiation. Competing Interests: Disclosures: The authors declare no competing interests exist. (This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.)
Databáze:	MEDLINE
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