MicroRNA-155 Promotes Autoimmune Inflammation by Enhancing Inflammatory T Cell Development

被引:842
作者
O'Connell, Ryan M. [1 ]
Kahn, Daniel [1 ,2 ]
Gibson, William S. J. [1 ]
Round, June L. [1 ]
Scholz, Rebecca L. [1 ]
Chaudhuri, Aadel A. [1 ]
Kahn, Melissa E. [4 ]
Rao, Dinesh S. [1 ,3 ]
Baltimore, David [1 ]
机构
[1] CALTECH, Div Biol, Pasadena, CA 91125 USA
[2] Univ Calif Los Angeles, Div Maternal Fetal Med, Dept Obstet & Gynecol, David Geffen Sch Med, Los Angeles, CA 90095 USA
[3] Univ Calif Los Angeles, Dept Pathol & Lab Med, David Geffen Sch Med, Los Angeles, CA 90095 USA
[4] Cedars Sinai Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90048 USA
基金
美国国家卫生研究院; 美国国家科学基金会;
关键词
CUTTING EDGE; TGF-BETA; DIFFERENTIATION; ACTIVATION; EXPRESSION; TARGET; ROLES; MICE; GENERATION; PATHWAY;
D O I
10.1016/j.immuni.2010.09.009
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Mammalian noncoding microRNAs (miRNAs) are a class of gene regulators that have been linked to immune system function Here, we have investigated the role of miR-155 during an autoimmune inflammatory disease Consistent with a positive role for mir155(-/-) in mediating inflammatory responses, Mir155(-/-) mice were highly resistant to experimental autoimmune encephalomyelitis (EAE) miR-155 functions in the hematopoietic compartment to promote the development of inflammatory T cells including the T helper 17 (Th17) cell and Th1 cell subsets Furthermore, the major contribution of miR-155 to EAE was CD4(+) T cell intrinsic, whereas miR-155 was also required for optimum dendritic cell production of cytokines that promoted Th17 cell formation Our study shows that one aspect of miR-155 function is the promotion of T cell-dependent tissue inflammation, suggesting that miR-155 might be a promising therapeutic target for the treatment of autoimmune disorders
引用
收藏
页码:607 / 619
页数:13
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