MicroRNAs Control the Maintenance of Thymic Epithelia and Their Competence for T Lineage Commitment and Thymocyte Selection
Zuklys, Saulius × Mayer, Carlos E Zhanybekova, Saule Stefanski, Heather E Nusspaumer, Gretel Gill, Jason Barthlott, Thomas Chappaz, Stephane Nitta, Takeshi Dooley, James Nogales-Cadenas, Ruben Takahama, Yousuke Finke, Daniela Liston, Adrian Blazar, Bruce R Pascual-Montano, Alberto Holländer, Georg A #
American Association of Immunologists
Journal of Immunology vol:189 issue:8 pages:3894-3904
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.