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    Home > Active Ingredient News > Immunology News > Immunity: Zhejiang University Jin Jin/Cao Qian team reveals a new mechanism by which trace element selenium regulates T cell differentiation

    Immunity: Zhejiang University Jin Jin/Cao Qian team reveals a new mechanism by which trace element selenium regulates T cell differentiation

    • Last Update: 2021-10-02
    • Source: Internet
    • Author: User
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    Inflammatory bowel disease (IBD) mainly includes Crohn's disease (CD) and ulcerative colitis (UC).
    It is a chronic intestinal disease caused by the imbalance of intestinal flora and intestinal immune system.
    It affects the quality of life of patients and currently cannot be cured, so it is also called "green cancer"
    .

    Genetic factors, disorder of the intestinal flora and imbalance of the intestinal mucosal immune system are the main causes of IBD, but the molecular mechanism of its pathogenicity is still unclear
    .

    The rapid development of single-cell sequencing (scRNA-seq) technology in recent years has allowed people to refine the exploration of disease pathogenesis to cell subgroups.
    Aviv Regev revealed that some known risk genes are involved in different cell types and signaling pathways in the intestinal mucosa of UC patients.
    Distribution [1], Marco Colonna et al.
    identified the unique T cell subpopulations in the inflammatory site of the terminal ileum in adult patients with severe CD [2].
    Athos Bousvaros et al.
    Colonic mucosal disease-specific immune cell population [3]
    .

    At present, patients included in these research projects have received drug treatment, and their intestinal immune microenvironment will be affected.
    Therefore, it is still to be studied for IBD patients who have not used drug treatment
    .

    On August 2, 2021, Jin Jin's research group from the Institute of Life Sciences of Zhejiang University and Cao Qian's research group from the Run Run Run Run Shaw Hospital of Zhejiang University jointly published the title: Multiomic analyses reveal a critical role of selenium in the top immunology journal Immunity.
    Research paper on in controlling T cell differentiation in Crohn's disease
    .

    The study identified disease-specific immune cell subsets and altered metabolites in newly diagnosed inflammatory bowel disease (IBD) patients, and analyzed the new mechanism of trace element selenium regulating the differentiation of type I helper T (Th1) cells, which is Crohn’s disease ( CD) treatment provides potential new targets
    .

    In this study, the researchers tested the colonic mucosal immunity of 3 healthy controls and 12 newly diagnosed patients who did not receive medication for moderate to severe Crohn's disease (CD) and ulcerative colitis (UC).
    Cells were single-cell sequencing.
    Through cluster analysis of 63314 high-quality transcriptome data, the researchers found that Th1-like cells and GPBhiFollicular B cells in newly diagnosed CD patients increased specifically, while Th17-like cells and exhausted Tc17 cells The proportion is specifically increased in newly diagnosed UC patients
    .

    By comparing the transcriptome levels of Th1-like and Th17-like cells, the researchers found changes in metabolism-related genes, and then speculated that metabolism may play an important role in the formation of differential patterns of T cell differentiation in CD and UC patients
    .

     In order to verify this conjecture, the researchers collected 30 control populations and 64 active IBD patients (32 cases of UC and CD patients) living tissue samples, and used LC-MS non-targeted metabolomics technology to identify the disease Specific changes in metabolites
    .

    Next, the researchers performed functional screening of disease-specific differential metabolites and found that adding the organic form of selenium 3'-phosphate adenylate to the medium significantly inhibited the differentiation of Th1 cells without affecting the differentiation of Th17 cells
    .

    In order to analyze the mechanism of selenium affecting T cell differentiation, the researchers used metabolomics technology to find the metabolite purine and its derivatives (adenine, xanthine, uric acid, etc.
    ) that were significantly up-regulated in Th1 cells induced by selenium
    .

    The synthesis of endogenous purine nucleotides is mainly through the re-synthesis and salvage pathway.
    Transcriptomics analysis shows that the increase in selenium content increases the activity of the purine synthesis salvage pathway in Th1 cells, while the purine resynthesis pathway is inhibited.
    At the same time, the researchers also It was found that the metabolism of one carbon and folic acid changed significantly
    .

     Uric acid is an effective antioxidant that can scavenge singlet oxygen and free radicals, suggesting that selenium may regulate the concentration of reactive oxygen species (ROS) by promoting purine synthesis to regulate the differentiation of Th1 cells
    .

    The researchers confirmed this conjecture and clarified that selenium regulates the differentiation of Th1 cells in CD patients by targeting the ROS-NF-κB axis.
    In addition, the researchers also found that one-carbon metabolism also plays an important role and negatively regulates the differentiation of Th1 cells.
    Purine salvage synthesis pathway
    .

    These findings provide many new targets for regulating the differentiation of Th1 cells
    .

     As a key trace element, selenium will form selenoprotein to play its role
    .

    In order to further explore the mechanism by which selenium regulates Th1 cell differentiation, the researchers used MS targeting selenocysteine ​​and found that increased selenium content promotes selenoprotein W (SELW), GPX1, GPX4, TRXR1, and selenoprotein W (SELW) during Th1 differentiation.
    The production of TRXR2
    .

    The researchers then clarified the key role of selenoprotein SLEW in the process of selenium regulating Th1 cell differentiation, and revealed that SELW regulates the purine salvage pathway and one-carbon metabolism by recruiting E3 ubiquitin link enzyme TRIM21 and a variety of metabolic enzymes.
    Specific mechanism
    .

    Finally, the researchers verified the effects of selenium in vivo using mouse enteritis models and clinical experiments in CD patients
    .

    In general, the research team used Crohn’s disease (CD) and ulcerative colitis (UC) patients who were newly diagnosed and had not used any drugs as the research subjects, with the help of single-cell sequencing, metabolomics, and protein profiling.
    It revealed disease-specific immune cell subgroups and changed metabolites, analyzed the molecular mechanism of selenium regulating Th1 cell differentiation, and provided a new theoretical basis for the pathogenesis of Crohn’s disease
    .

    In addition, the study also found that the combination of therapeutic drugs and selenium supplements can effectively alleviate the symptoms of colitis in patients with Crohn's disease, providing new insights for the treatment of Crohn's disease
    .

     Link to the paper: https:// Open for reprint 
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