國家衛生研究院 NHRI:Item 3990099045/13547
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    题名: Induction of interferon-gamma and tissue inflammation by overexpression of eosinophil cationic protein in T cells and exosomes
    其它题名: Induction of interferon-γ and tissue inflammation by overexpression of eosinophil cationic protein in T cells and exosomes
    作者: Chuang, HC;Chen, MH;Chen, YM;Ciou, YR;Hsueh, CH;Tsai, CY;Tan, TH
    贡献者: Immunology Research Center
    摘要: OBJECTIVES: T cells play critical roles in the pathogenesis of systemic lupus erythematosus (SLE). Serum-derived exosomes are increased in SLE patients and are correlated with disease severity. The proteins in the T-cell-derived exosomes from SLE patients could play important roles in SLE pathogenesis. METHODS: We characterized proteins of SLE T cell-derived exosomes by exosome MACSPlex analysis and proteomics using T-cell supernatants from SLE patients and healthy controls. To study the potential pathogenic functions of the identified exosomal protein, we generated and characterized T-cell-specific transgenic mice that overexpressed the identified protein in T cells. RESULTS: We identified eosinophil cationic protein (ECP, also named human RNase 3) that was overexpressed in SLE T cell-derived exosomes. T-cell-specific ECP transgenic mice displayed early induction of serum IFN-γ levels and multi-tissue inflammation. The aged T-cell-specific ECP transgenic mice also displayed an increase of follicular helper T cells, plasma B cell, and autoantibodies. Single-cell RNA sequencing (scRNA-seq) also showed the induction of IFN-γ mRNA and inflammatory pathways in ECP transgenic T cells. Remarkably, adoptively transferred ECP-containing exosomes stimulated serum levels of IFN-γ and autoantibodies in the recipient mice. The transferred exosomes infiltrated into multiple tissues of the recipient mice, resulting in hepatitis, nephritis, and arthritis. CONCLUSIONS: ECP overexpression in T cells or T-cell-derived exosomes may be a biomarker and pathogenic factor for human SLE nephritis, hepatitis, and arthritis.
    日期: 2022-01
    關聯: Arthritis and Rheumatology. 2022 Jan;74(1):92-104.
    Link to: http://dx.doi.org/10.1002/art.41920
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2326-5191&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000728315000001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85119345260
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