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    Home > Active Ingredient News > Immunology News > ​Nat Immunol Xue Haihui/Zang Chongzhi's team discovered the important regulatory role of Tcf1 transcription factor in T cell immune memory and secondary immune response

    ​Nat Immunol Xue Haihui/Zang Chongzhi's team discovered the important regulatory role of Tcf1 transcription factor in T cell immune memory and secondary immune response

    • Last Update: 2022-05-01
    • Source: Internet
    • Author: User
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    Editor-in-Chief | After the immune system has an immune response to the bacteria or viruses that have invaded the body, the next time it encounters the same bacteria or viruses, it will still recognize and stimulate the immune response again.
    This process is called immune memory and secondary immune response
    .

    An in-depth understanding of the molecular mechanisms of immune memory and secondary immune responses will help to develop vaccines with higher levels of protection and more advanced tumor immunotherapy in the future
    .

    Memory immune cells are the basis of immune memory and secondary responses.
    How transcription factors and epigenetic factors regulate gene expression during the differentiation and activation of various immune cells has always been a concern of immunologists and molecular biologists
    .

    On February 21, 2022, the team of Professor Haihui Xue from Hackensack University Medical Center and the team of Professor Zang Chongzhi from the University of Virginia jointly published a paper entitled Tcf1 preprograms the mobilization of glycolysis in Nature Immunology The research paper in central memory CD8+ T cells during recall responses revealed the mechanism by which transcription factor Tcf1 regulates gene transcription during the secondary immune response of a memory immune cell.
    In particular, it was found that Tcf1 preprograms sugars by regulating the three-dimensional genome.
    Transcriptional enhancers of functional genes such as glycolysis, the ability to activate gene expression after mobilizing secondary responses
    .

    CD8+ T cells are an important class of immune cells that play an important role in the cellular immune response against infection and tumor
    .

    After acute infection by pathogens, a portion of antigen-specific CD8+ T cells differentiate into CD8+ memory T cells
    .

    CD8+ memory T cells are composed of multiple subsets, mainly including CD8+ effector memory T cells (TEM) and CD8+ central memory T cells (TCM) in the circulating system
    .

    Among them, TCMs have stronger self-renewal capacity and proliferate more rapidly when re-stimulated, and are the main subgroup for long-lasting immune protection
    .

    Tcf1 belongs to the HMG (high mobility group) transcription factor.
    Previous studies have found that Tcf1 determines the persistence and secondary response ability of CD8+ memory T cells
    .

    The work published this time is mainly to answer the question of the mechanism of Tcf1 regulating the secondary response
    .

    The researchers firstly determined that Tcf1 deletion affects the secondary immune response ability of TCM subsets, but has little effect on TEM subsets
    .

    During the secondary immune response, by comparing the transcriptomic and epigenetic data of TCM cells in mice before and after Tcf1 knockout, the researchers found that Tcf1 deletion had less effect on TCM gene expression in the resting state After activation, the expression levels of genes related to glycolysis process, cell proliferation and other functions are insufficiently increased, the degree of chromatin opening is low, and the function is also unable to effectively remove infected pathogens
    .

    Tcf1 is abundantly expressed in CD8+ naive T cells and CD8+ memory T cells, while Tcf1 expression levels decrease rapidly after T cell receptor (TCR) activation
    .

    Therefore, the effect of Tcf1 on the secondary immune response of TCM should be in the TCM stage before TCR activation
    .

    The researchers found through ChIP-seq experiments that Tcf1 binds around many genes associated with secondary responses in TCM cells
    .

    Using three-dimensional genome Hi-C analysis, the researchers further found that Tcf1 mediates special chromatin interactions around functional genes, pulling the promoters and enhancers of key secondary response genes including glycolysis functional genes closer distance between children
    .

    When the secondary response occurs, transcription factors such as NFAT and AP1 are bound around the functional genes mediated by Tcf1, effectively promoting the expression efficiency of the secondary response-related genes
    .

    Thus, Tcf1 preprograms a gene transcriptional activation program affecting glycolysis as well as cell proliferation in TCM and can be stimulated upon TCR activation
    .

    This finding enriches the understanding of Tcf1 regulation of gene expression and reveals the molecular mechanism of Tcf1 in promoting the secondary immune response of TCM
    .

    Professor Xue Haihui and Professor Zang Chongzhi are the co-corresponding authors of this article
    .

    Dr.
    Shan Qiang from Xue Haihui's research group and Dr.
    Hu Shengen from Zang Chongzhi's research group are the co-first authors of this paper
    .

    Attached recruitment advertisement: Professor Zang Chongzhi's research group at the University of Virginia recruits postdoctoral and doctoral students in the direction of bioinformatics/computational biology for a long time.
    Original link: https:// 11.
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