MicroRNAs control the maintenance of thymic epithelia and their competence for T lineage commitment and thymocyte selection

Saulius Zuklys, Carlos E. Mayer, Saule Zhanybekova, Heather E. Stefanski, Gretel Nusspaumer, Jason Gill, Thomas Barthlott, Stephane Chappaz, Takeshi Nitta, James Dooley, Ruben Nogales-Cadenas, Yousuke Takahama, Daniela Finke, Adrian Liston, Bruce R. Blazar, Alberto Pascual-Montano, Georg A. Hollände

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3894-3904
Number of pages11
JournalJournal of Immunology
Volume189
Issue number8
DOIs
StatePublished - Oct 15 2012

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