Journal article
Tcf1 preprograms the mobilization of glycolysis in central memory CD8 + T cells during recall responses
Nature immunology, Vol.23(3), pp.386-398
02/21/2022
DOI: 10.1038/s41590-022-01131-3
PMCID: PMC8904300
PMID: 35190717
Abstract
The mechanisms underlying the heightened protection mediated by central memory CD8+ T (TCM) cells remain unclear. Here we show that the transcription factor Tcf1 was required in resting TCM cells to generate secondary effector CD8+ T cells and to clear pathogens during recall responses. Recall stimulation of CD8+ TCM cells caused extensive reprogramming of the transcriptome and chromatin accessibility, leading to rapid induction of glycolytic enzymes, cell cycle regulators and transcriptional regulators, including Id3. This cluster of genes did not require Tcf1 in resting CD8+ TCM cells, but depended on Tcf1 for optimal induction and chromatin opening in recall-stimulated CD8+ TCM cells. Tcf1 bound extensively to these recall-induced gene loci in resting CD8+ TCM cells and mediated chromatin interactions that positioned these genes in architectural proximity with poised enhancers. Thus, Tcf1 preprogramed a transcriptional program that supported the bioenergetic and proliferative needs of CD8+ TCM cells in case of a secondary challenge.
Details
- Title: Subtitle
- Tcf1 preprograms the mobilization of glycolysis in central memory CD8 + T cells during recall responses
- Creators
- Qiang Shan - Center for Discovery and Innovation, Hackensack University Medical Center, Nutley, NJ, USAShengen Shawn Hu - Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, VA, USAShaoqi Zhu - Department of Physics, The George Washington University, Washington, DC, USAXia Chen - Center for Discovery and Innovation, Hackensack University Medical Center, Nutley, NJ, USAVladimir P Badovinac - Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA, USAWeiqun Peng - Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, VA, USAChongzhi Zang - Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA. zang@virginia.eduHai-Hui Xue - New Jersey Veterans Affairs Health Care System, East Orange, NJ, USA. haihui.xue@hmh-cdi.org
- Resource Type
- Journal article
- Publication Details
- Nature immunology, Vol.23(3), pp.386-398
- DOI
- 10.1038/s41590-022-01131-3
- PMID
- 35190717
- PMCID
- PMC8904300
- NLM abbreviation
- Nat Immunol
- eISSN
- 1529-2916
- Grant note
- AI121080 / U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) AI139874 / U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) AI112579 / U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) AI114543 / U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) GM134880 / U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)
- Language
- English
- Date published
- 02/21/2022
- Academic Unit
- Microbiology and Immunology; Pathology
- Record Identifier
- 9984221759602771
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