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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.

Original publication

DOI

10.4049/jimmunol.1200783

Type

Journal article

Journal

J Immunol

Publication Date

15/10/2012

Volume

189

Pages

3894 - 3904

Keywords

Animals, Cell Differentiation, Cell Lineage, DEAD-box RNA Helicases, Epithelial Cells, Mice, Mice, Nude, Mice, Transgenic, MicroRNAs, Mutation, Organ Culture Techniques, Ribonuclease III, Stromal Cells, T-Lymphocytes, Thymus Gland