Regulation of Memory T Cells in the 3D Space

ABSTRACT

CD62L+ central memory CD8+T (T CM) cells provide enhanced protection than naïve cells; however, the underlying mechanism, especially the contribution of higher-order genomic organization, remains unclear. Systematic Hi-C analyses reveal that antigen-experienced CD8+ T cells undergo extensive rewiring of chromatin interactions, with T CM cells harboring specific interaction hubs compared with naïve CD8+ T cells, as observed at cytotoxic effector genes such as Ifng and Tbx21. T CM cells also acquire de novo CTCF binding sites, which are not only strongly associated with T CM-specific hubs but also linked to increased activities of local gene promoters and enhancers. Specific ablation of CTCF in T CM cells impairs rapid induction of genes in cytotoxic program, energy supplies, transcription, and translation by recall stimulation. Therefore, acquisition of CTCF binding and chromatin interaction hubs by T CM cells serves as a chromatin architectural basis for their transcriptomic dynamics in primary response and for imprinting the code of “recall readiness” against secondary challenge.

BIOGRAPHY

Dr. Hai-Hui Xue received his M.D. from China Medical University in 1991, and his PhD in Biochemistry from Hamamatsu University School of Medicine, Japan in 2000. He received postdoctoral training in molecular immunology at the NHLBI, and started to lead his own independent group at the University of Iowa in 2006. He joined the faculty at the Center for Discovery and Innovation, Hackensack University Medical Center in 2020. Dr. Xue’s lab has been employing state-of-the-art techniques including mouse genetics, molecular biology, cellular immunology, high throughput genomics and bioinformatics approaches to delineate transcriptional and epigenetic regulation of T cell biology. His research programs are supported by the NIH and Department of Veteran Affairs, USA.

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