羟氯喹通过核因子活化T细胞（NFAT）而非信号转导子和转录激活子5（STAT5）信号通路抑制系统性红斑狼疮患者CD4 T淋巴细胞中CD154的表达。

Hydroxychloroquine inhibits CD154 expression in CD4 T lymphocytes of systemic lupus erythematosus through NFAT, but not STAT5, signaling.

作者信息

Wu Shu-Fen, Chang Chia-Bin, Hsu Jui-Mei, Lu Ming-Chi, Lai Ning-Sheng, Li Chin, Tung Chien-Hsueh

机构信息

Department of Life Science, Institute of Molecular Biology, National Chung-Cheng University, No.168, University Rd, Min-Hsiung, Chia-Yi, 62247, Taiwan.

Division of Allergy, Immunology and Rheumatology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi, Taiwan.

出版信息

Arthritis Res Ther. 2017 Aug 9;19(1):183. doi: 10.1186/s13075-017-1393-y.

BACKGROUND

Overexpression of membranous CD154 in T lymphocytes has been found previously in systemic lupus erythematosus (SLE). Because hydroxychloroquine (HCQ) has been used frequently in the treatment of lupus, we sought to identify the effects of HCQ on CD154 and a possibly regulatory mechanism.

METHODS

CD4 T cells were isolated from the blood of lupus patients. After stimulation with ionomycin or IL-15 and various concentrations of HCQ, expression of membranous CD154 and NFAT and STAT5 signaling were assessed.

RESULTS

HCQ treatment had significant dose-dependent suppressive effects on membranous CD154 expression in ionomycin-activated T cells from lupus patients. Furthermore, HCQ inhibited intracellular sustained calcium storage release, and attenuated the nuclear translocation of NFATc2 and the expression of NFATc1. However, CD154 expressed through IL-15-mediated STAT5 signaling was not inhibited by HCQ treatment.

CONCLUSIONS

HCQ inhibited NFAT signaling in activated T cells and blocked the expression of membranous CD154, but not STAT5 signaling. These findings provide a mechanistic insight into SLE in HCQ treatment.