Dicer-dependent microRNA pathway safeguards regulatory T cell function

被引:332
作者
Liston, Adrian [1 ,2 ,3 ]
Lu, Li-Fan [1 ,2 ]
O'Carroll, Donal [4 ]
Tarakhovsky, Alexander [4 ]
Rudensky, Alexander Y. [1 ,2 ]
机构
[1] Univ Washington, Dept Immunol, Seattle, WA 98195 USA
[2] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA
[3] Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT 0200, Australia
[4] Rockefeller Univ, Lab Lymphocyte Signaling, New York, NY 10065 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1084/jem.20081062
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Regulatory T (T reg) cells are indispensable for preventing autoimmunity. Incumbent to this role is the ability of T reg cells to exert their suppressor function under inflammatory conditions. We found that T reg cell-mediated tolerance is critically dependent on the Dicer-controlled microRNA (miRNA) pathway. Depletion of miRNA within the T reg cell lineage resulted in fatal autoimmunity indistinguishable from that in T reg cell-deficient mice. In disease-free mice lacking Dicer in all T cells or harboring both Dicer-deficient and -sufficient T reg cells, Dicer-deficient T reg cells were suppressive, albeit to a lesser degree, whereas their homeostatic potential was diminished as compared with their Dicer-sufficient counterparts. However, in diseased mice, Dicer-deficient T reg cells completely lost suppressor capacity. Thus, miRNA preserve the T reg cell functional program under inflammatory conditions.
引用
收藏
页码:1993 / 2004
页数:12
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