國家衛生研究院 NHRI:Item 3990099045/12670
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    题名: MAP4K3/GLK-induced AhR-RORyt complex is a novel therapeutic target for GLIC(high)IL-17A(high) subpopulation of SLE patients
    作者: Chuang, HC;Tan, TH
    贡献者: Immunology Research Center
    摘要: The cytokine IL-17A plays critical roles in the pathogenesis of autoimmune diseases. The frequencies of MAP4K3 (also named GLK)-overexpressing T cells are correlated with disease severity of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and adult-onset Still’s disease. T-cell specific GLK transgenic mice develop spontaneous autoimmune responses. GLK signaling selectively stimulates IL-17A production in murine T cells through inducing AhR-RORγt complex formation. Here, we investigated whether GLK-induced AhR-RORγt complex in T cell is a therapeutic target for human SLE or RA. The population of GLK+IL-17A+ T cells was enhanced in the peripheral blood from SLE patients compared to that of healthy controls using flow cytometry. The ROC curve analyses showed that increased GLK+IL-17A+ T cell population in peripheral blood reflected an active stage of SLE. In addition, peripheral blood T cells from SLE or RA patients displayed induction of RORγt phosphorylation and the AhR-RORγt complex. Moreover, we identified a small-molecule GLK inhibitor that inhibited GLK kinase activity and AhR-RORγt interaction. The GLK inhibitor suppressed the disease severity in autoimmune mouse models and IL-17A production in T cells from SLE or RA patients. Collectively, GLK-induced AhR-RORγt complex is a therapeutic target for the GLKhighIL-17Ahigh subpopulation of SLE or RA patients.
    日期: 2019-05
    關聯: Journal of Immunology. 2019 May;202(1, Suppl. S):Meeting Abstract 132.2.
    Link to: https://www.jimmunol.org/content/202/1_Supplement/132.2
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0022-1767&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000524982501129
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