title: MicroRNAs control the maintenance of thymic epithelia and their competence for T lineage commitment and thymocyte selection.
abstract: Thymic epithelial cells provide unique cues for the lifelong selection and differentiation of a repertoire of functionally diverse T cells. Rendered microRNA (miRNA) deficient, these stromal cells in the mouse lose their capacity to instruct the commitment of hematopoietic precursors to a T cell fate, to effect thymocyte positive selection, and to achieve promiscuous gene expression required for central tolerance induction. Over time, the microenvironment created by miRNA-deficient thymic epithelia assumes the cellular composition and structure of peripheral lymphoid tissue, where thympoiesis fails to be supported. These findings emphasize a global role for miRNA in the maintenance and function of the thymic epithelial cell scaffold and establish a novel mechanism how these cells control peripheral tissue Ag expression to prompt central immunological tolerance.
authors.affiliation: Laboratory of Pediatric Immunology, Department of Biomedicine, University of Basel and Basel University Children's Hospital, Basel 4031, Switzerland.
authors.forename: Saulius
authors.initials: S
authors.lastname: Zuklys
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Mayer
authors.forename: Saule
authors.initials: S
authors.lastname: Zhanybekova
authors.forename: Heather E
authors.initials: HE
authors.lastname: Stefanski
authors.forename: Gretel
authors.initials: G
authors.lastname: Nusspaumer
authors.forename: Jason
authors.initials: J
authors.lastname: Gill
authors.forename: Thomas
authors.initials: T
authors.lastname: Barthlott
authors.forename: Stephane
authors.initials: S
authors.lastname: Chappaz
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nitta
authors.forename: James
authors.initials: J
authors.lastname: Dooley
authors.forename: Ruben
authors.initials: R
authors.lastname: Nogales-Cadenas
authors.forename: Yousuke
authors.initials: Y
authors.lastname: Takahama
authors.forename: Daniela
authors.initials: D
authors.lastname: Finke
authors.forename: Adrian
authors.initials: A
authors.lastname: Liston
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Blazar
authors.forename: Alberto
authors.initials: A
authors.lastname: Pascual-Montano
authors.forename: Georg A
authors.initials: GA
authors.lastname: Holländer
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology*; D053487:DEAD-box RNA Helicases / Q000172:deficiency; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000502:physiology*; D009154:Mutation; D009924:Organ Culture Techniques; D043244:Ribonuclease III / Q000172:deficiency; D017154:Stromal Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000196:embryology / Q000276:immunology* / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases