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

被引：85

作者：

Xin, Qian ^{[1
,2
]}

Li, Jiangxia ^{[1
,2
]}

Dang, Jie ^{[1
,2
]}

Bian, Xianli ^{[1
,2
]}

Shan, Shan ^{[1
,2
]}

Yuan, Jupeng ^{[1
,2
]}

Qian, Yanyan ^{[1
,2
]}

Liu, Zhaojian ^{[3
]}

Liu, Guangyi ^{[4
]}

Yuan, Qianqian ^{[1
,2
]}

Ma, Xiaochun ^{[1
,2
]}

Gao, Fei ^{[1
,2
]}

Gong, Yaoqin ^{[1
,2
]}

Liu, Qiji ^{[1
,2
]}

机构：

[1] Shandong Univ, Sch Med, Key Lab Expt Teratol, Minist Educ, Jinan 250012, Shandong, Peoples R China

[2] Shandong Univ, Sch Med, Dept Med Genet, Jinan 250012, Shandong, Peoples R China

[3] Shandong Univ, Sch Med, Dept Cell Biol, Jinan 250012, Shandong, Peoples R China

[4] Shandong Univ, Dept Nephrol, Qilu Hosp, Jinan 250012, Shandong, Peoples R China

来源：

JOURNAL OF IMMUNOLOGY | 2015年 / 194卷 / 11期

关键词：

REGULATORY T-CELLS; PROINFLAMMATORY REGULATOR; MICRORNA-155; SPHINGOSINE-1-PHOSPHATE; ARTHRITIS; PATHOGENESIS; RESPONSES; CANCER; IL-17;

D O I：

10.4049/jimmunol.1403028

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

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 Fas(lpr/lpr) (miR-155(-/-) Fas(lpr/lpr)) mice were obtained by crossing miR-155(-/-) and Fas(lpr/lpr) mice. Clinical SLE features such as glomerulonephritis, autoantibody levels, and immune system cell populations were compared between miR-155(-/-) Fas(lpr/lpr) and Fas(lpr/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(-/-) Fas(lpr/lpr) mice showed milder SLE clinical features than did Fas(lpr/lpr) mice. As compared with Fas(lpr/lpr) mice, miR-155(-/-) Fas(lpr/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(-/-) Fas(lpr/lpr) than Fas(lpr/lpr) mice; the CD4(+)/CD8(+) T cell ratio was restored in miR-1552/2 Fas(lpr/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 Fas(lpr/lpr) mice. miR-155(-/-) Fas(lpr/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.

引用

页码：5437 / 5445

页数：9

共 32 条

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SPONTANEOUS MURINE LUPUS-LIKE SYNDROMES - CLINICAL AND IMMUNOPATHOLOGICAL MANIFESTATIONS IN SEVERAL STRAINS [J].