國家衛生研究院 NHRI:Item 3990099045/15970
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    NHRI > Immunology Research Center > Yu-Wen Su > Periodical Articles >  Item 3990099045/15970


    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/15970


    Title: PTEN acts as a crucial inflammatory checkpoint controlling TLR9/IL-6 axis in B cells
    Authors: Tsai, PJ;Chen, MY;Hsu, WC;Lin, SF;Chan, PC;Chen, HH;Kao, CY;Lin, WJ;Chuang, TH;Yu, GY;Su, YW
    Contributors: Immunology Research Center;National Institute of Cancer Research;National Institute of Infectious Diseases and Vaccinology
    Abstract: Phosphatase and tensin homolog (PTEN) is vital for B cell development, acting as a key negative regulator in the PI3K signaling pathway. We used CD23-cre to generate PTEN-conditional knockout mice (CD23cKO) to examine the impact of PTEN mutation on peripheral B cells. Unlike mb1-cre-mediated PTEN deletion in early B cells, CD23-cKO mutants exhibited systemic inflammation with increased IL-6 production in mature B cells upon CpG stimulation. Inflammatory B cells in CD23-cKO mice showed elevated phosphatidylinositol 3-phosphate [PI(3)P] levels and increased TLR9 endosomal localization. Pharmacological inhibition of PI(3)P synthesis markedly reduced TLR9-mediated IL-6. Single-cell RNA-sequencing (RNA-seq) revealed altered endocytosis, BANK1, and NF- K B1 expression in PTEN-deficient B cells. Ectopic B cell receptor (BCR) expression on non-inflammatory mb1-cKO B cells restored BANK1 and NF- K B1 expression, enhancing TLR9-mediated IL-6 production. Our study highlights PTEN as a crucial inflammatory checkpoint, regulating TLR9/IL-6 axis by fine-tuning PI(3)P homeostasis. Additionally, BCR downregulation prevents the differentiation of inflammatory B cells in PTEN deficiency.
    Date: 2024-07-19
    Relation: iScience. 2024 Jul 19;27(7):Article number 110388.
    Link to: http://dx.doi.org/10.1016/j.isci.2024.110388
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2589-0042&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:001268378400001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85198146375
    Appears in Collections:[Yu-Wen Su] Periodical Articles
    [Tsung-Hsien Chuang] Periodical Articles
    [Wen-Jye Lin] Periodical Articles
    [Cheng-Yuan Gao] Periodical Articles
    [Su-Fang Lin] Periodical Articles
    [Guann-Yi Yu] Periodical Articles

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