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

• Published in: Arthritis research & therapy Vol. 19; no. 1; p. 183
• Main Authors: Wu, Shu-Fen, Chang, Chia-Bin, Hsu, Jui-Mei, Lu, Ming-Chi, Lai, Ning-Sheng, Li, Chin, Tung, Chien-Hsueh
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 09.08.2017; BioMed Central; BMC
• Subjects: Adult; Antirheumatic Agents - pharmacology; Care and treatment; CD154; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - metabolism; CD40 Ligand - antagonists & inhibitors; CD40 Ligand - metabolism; Cells, Cultured; Complications and side effects; Dosage and administration; Female; Humans; Hydroxychloroquine; Hydroxychloroquine - pharmacology; Jurkat Cells; Lupus Erythematosus, Systemic - blood; Lupus Erythematosus, Systemic - metabolism; Male; Middle Aged; NFAT; NFATC Transcription Factors - metabolism; Signal Transduction - drug effects; STAT5; STAT5 Transcription Factor - metabolism; Systemic lupus erythematosus; Young Adult; CD154; STAT5; Hydroxychloroquine; Systemic lupus erythematosus; NFAT
• ISSN: 1478-6362; 1478-6354; 1478-6362
• DOI: 10.1186/s13075-017-1393-y

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. 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. 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. 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.