title: The thymic epithelial microRNA network elevates the threshold for infection-associated thymic involution via miR-29a mediated suppression of the IFN-α receptor.
abstract: 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 epithelium, expression of the IFN-α receptor by the thymic epithelium was higher, which allowed suboptimal signals to trigger rapid loss of thymic cellularity.
authors.affiliation: VIB, Leuven, Belgium.
authors.forename: Aikaterini S
authors.initials: AS
authors.lastname: Papadopoulou
authors.forename: James
authors.initials: J
authors.lastname: Dooley
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Linterman
authors.forename: Wim
authors.initials: W
authors.lastname: Pierson
authors.forename: Olga
authors.initials: O
authors.lastname: Ucar
authors.forename: Bruno
authors.initials: B
authors.lastname: Kyewski
authors.forename: Saulius
authors.initials: S
authors.lastname: Zuklys
authors.forename: Georg A
authors.initials: GA
authors.lastname: Hollander
authors.forename: Patrick
authors.initials: P
authors.lastname: Matthys
authors.forename: Daniel H D
authors.initials: DH
authors.lastname: Gray
authors.forename: Bart
authors.initials: B
authors.lastname: De Strooper
authors.forename: Adrian
authors.initials: A
authors.lastname: Liston
mesh_terms: D000818:Animals; D001168:Arthritis / Q000235:genetics / Q000276:immunology; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000276:immunology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000276:immunology*; D053633:Receptor, Interferon alpha-beta / Q000276:immunology*; D043244:Ribonuclease III / Q000235:genetics / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
chemical_list: D051858:Forkhead Transcription Factors; C547014:MIRN29 microRNA, mouse; D035683:MicroRNAs; C090140:Whn protein; D053633:Receptor, Interferon alpha-beta; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases