MicroRNAs control the maintenance of thymic epithelia and their competence for T lineage commitment and thymocyte selection.
Zuklys S., Mayer CE., Zhanybekova S., Stefanski HE., Nusspaumer G., Gill J., Barthlott T., Chappaz S., Nitta T., Dooley J., Nogales-Cadenas R., Takahama Y., Finke D., Liston A., Blazar BR., Pascual-Montano A., Holländer GA.
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.