The thymic epithelial microRNA network elevates the threshold for infection-associated thymic involution via miR-29a mediated suppression of the IFN-α receptor

被引:145
作者
Papadopoulou, Aikaterini S. [1 ,2 ]
Dooley, James [1 ,3 ]
Linterman, Michelle A. [4 ,5 ]
Pierson, Wim [1 ,3 ]
Ucar, Olga [6 ]
Kyewski, Bruno [6 ]
Zuklys, Saulius [7 ]
Hollander, Georg A. [7 ]
Matthys, Patrick [8 ]
Gray, Daniel H. D. [9 ]
De Strooper, Bart [1 ,2 ]
Liston, Adrian [1 ,3 ]
机构
[1] VIB, Louvain, Belgium
[2] Katholieke Univ Leuven, Ctr Human Genet, Louvain, Belgium
[3] Katholieke Univ Leuven, Autoimmune Genet Lab, Louvain, Belgium
[4] Univ Cambridge, Cambridge Inst Med Res, Cambridge, England
[5] Univ Cambridge, Dept Med, Cambridge CB2 2QQ, England
[6] German Canc Res Ctr, D-6900 Heidelberg, Germany
[7] Univ Basel, Basel, Switzerland
[8] Katholieke Univ Leuven, Rega Inst, Immunobiol Lab, Louvain, Belgium
[9] Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia
基金
欧洲研究理事会; 英国医学研究理事会;
关键词
POSITIVE SELECTION; T-CELLS; DICER; DIFFERENTIATION; MICE; ACTIVATION; EXPRESSION; ABSENCE;
D O I
10.1038/ni.2193
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Thymic output is a dynamic process, with high activity at birth punctuated by transient periods of involution during infection. Interferon-alpha (IFN-alpha) is a critical molecular mediator of pathogen-induced thymic involution, yet despite the importance of thymic involution, relatively little is known about the molecular integrators that establish sensitivity. Here we found that the microRNA network dependent on the endoribonuclease Dicer, and specifically microRNA miR-29a, was critical for diminishing the sensitivity of the thymic epithelium to simulated infection signals, protecting the thymus against inappropriate involution. In the absence of Dicer or the miR-29a cluster in the thymic epithelium, expression of the IFN-a receptor by the thymic epithelium was higher, which allowed suboptimal signals to trigger rapid loss of thymic cellularity.
引用
收藏
页码:181 / 187
页数:7
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