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miR-155 Deficiency Ameliorates Autoimmune Inflammation of Systemic Lupus Erythematosus by Targeting S1pr1 in Faslpr/lpr Mice

2015; American Association of Immunologists; Volume: 194; Issue: 11 Linguagem: Inglês

10.4049/jimmunol.1403028

1550-6606

Qian Xin, Jiangxia Li, Jie Dang, Xianli Bian, Shan Shan, Jupeng Yuan, Yanyan Qian, Zhaojian Liu, Guangyi Liu, Qianqian Yuan, Na Liu, Xiaochun Ma, Fei Gao, Yaoqin Gong, Qiji Liu,

interferon and immune responses

Abstract MicroRNA-155 (miR-155) was previously found involved in the development of systemic lupus erythematosus (SLE) and other autoimmune diseases and the inflammatory response; however, the detailed mechanism of miR-155 in SLE is not fully understood. To explore the in vivo role of miR-155 in the pathogenesis of SLE, miR-155–deficient Faslpr/lpr (miR-155−/−Faslpr/lpr) mice were obtained by crossing miR-155−/− and Faslpr/lpr mice. Clinical SLE features such as glomerulonephritis, autoantibody levels, and immune system cell populations were compared between miR-155−/−Faslpr/lpr and Faslpr/lpr mice. Microarray analysis, RT-PCR, Western blot, and luciferase reporter gene assay were used to identify the target gene of miR-155. miR-155−/−Faslpr/lpr mice showed milder SLE clinical features than did Faslpr/lprmice. As compared with Faslpr/lpr mice, miR-155−/−Faslpr/lpr mice showed less deposition of total IgA, IgM, and IgG and less infiltration of inflammatory cells in the kidney. Moreover, the serum levels of IL-4 and IL-17a, secreted by Th2 and Th17 cells, were lower in miR-155−/−Faslpr/lpr than Faslpr/lpr mice; the CD4+/CD8+ T cell ratio was restored in miR-155−/−Faslpr/lpr mice as well. Sphingosine-1-phosphate receptor 1 (S1PR1) was found as a new target gene of miR-155 by in vitro and in vivo studies; its expression was decreased in SLE patients and Faslpr/lpr mice. miR-155−/−Faslpr/lpr mice are resistant to the development of SLE by the regulation of the target gene S1pr1. miR-155 might be a new target for therapeutic intervention in SLE.