國家衛生研究院 NHRI:Item 3990099045/12670

NHRI > Immunology Research Center > Huai-Chia Chuang > Conference Papers/Meeting Abstract > Item 3990099045/12670

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/12670

Title:	MAP4K3/GLK-induced AhR-RORyt complex is a novel therapeutic target for GLIC(high)IL-17A(high) subpopulation of SLE patients
Authors:	Chuang, HC;Tan, TH
Contributors:	Immunology Research Center
Abstract:	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.
Date:	2019-05
Relation:	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
Appears in Collections:	[Huai-Chia Chuang] Conference Papers/Meeting Abstract [Tse-Hua Tan] Conference Papers/Meeting Abstract

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