Gene regulation is one of the most fundamental mechanisms governing cell 62functions and biological processes, including immune cells and the im-mune system. Recent advances in profiling the epigenome and transcriptome, leveraging next-generation sequencing (NGS), have enabled us to investigate gene regulation in an unprecedented manner, thereby uncovering previously uncharted molecular mechanisms in biology and immunology.Our research aims to enhance the understanding of gene regulation in im-mune cells and the immune system to improve the diagnosis and treatment of immune disorders. While transcriptomic analysis can be applied to various stud-ies in immunological contexts, our interest has particularly been in 1) studies of immune tolerance and 2) a project for the systematic analysis of immunocytes.Molecular mechanisms for immune toleranceTo establish immune tolerance, self-reactive T cells are either eliminated (i.e., negative selection) or diverted into regulatory T cells (T regs) in the thy-mus during development. Among the various cell populations involved in this process, thymic medullary epithelial cells (mTECs) play a unique role by ec-topically expressing tissue-restricted self-antigens (TRAs). Since the expression of TRAs is essential for discriminating between self and non-self and for estab-lishing self-tolerance, the expression of TRAs has been central in the studies of mTECs. However, given the complexity of the processes of negative selection and induction of T regs, it is worthwhile to consider the roles of mTECs beyond the expression of TRAs. By utilizing detailed transcriptome analysis of mTECs, we have been able to identify, in an unbiased manner, candidate genes linked to immune tolerance. To validate their significance, we have established appropri-ate mouse models, which are currently under investigation.Systematic analysis of the immune system employing a data-driven ap-proach.Bioinformatics has significantly impacted research on gene regulation and has become increasingly powerful with the advent of big data analysis. To ad-vance data-driven studies, we are collaborating with the ImmGen group.Figure: Immunofluorescence analysis of a mouse thymic tissue sectionThe green color indicates thymocytes that are in the process of dying through apoptosis. This occurs as the thymus filters out cells that react against self, a process known as “negative selection.” The red staining denotes CD90, which is characteristic of thymocytes, while the dotted line indicates the medullary border.YCI Laboratory for Immunological TranscriptomicsYoung Chief Investigator: Hideyuki Yoshida
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