The thymic epithelial microRNA network elevates the threshold for infection-associated thymic involution via miR-29a mediated suppression of the IFN-alpha receptor
Aikaterini S Papadopoulou, James Dooley, Michelle A Linterman, Wim Pierson, Olga Ucar, Bruno Kyewski, Saulius Zuklys, Georg A Hollander, Patrick Matthys, Daniel HD Gray, Bart De Strooper, Adrian Liston
Nature Immunology | NATURE PUBLISHING GROUP | Published : 2012
Thymic output is a dynamic process, with high activity at birth punctuated by transient periods of involution during infection. Interferon-α (IFN-α) 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 epitheli..View full abstract
Awarded by NATIONAL INSTITUTE ON AGING
We thank A. Tarakhovsky (Rockefeller University) for Dicer<SUP>fl</SUP> mice; N. Manley (University of Georgia) for Foxn1<SUP>Cre</SUP> mice; A. Farr (University of Washington) for hybridomas; S. Schonefeldt for mouse colony support and D. Anz for discussions. Supported by the VIB and Fonds Wetenschappelijk Onderzoek (A. L.), Methusalem financing (KULeuven and Flemish government), European Research Council (B. D. S.), Agentschap voor Innovtie door Wetenschap en Technologie (W. P.), the Australian National Health and Medical Research Council (D. H. D. G.), the European Union consortium "Tolerage" and the Deutsches Krebsforschungszentrum (B. K.).