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

MicroRNAs control the maintenance of thymic epithelia and their competence for T lineage commitment and thymocyte selection.
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DOI:
10.4049/jimmunol.1200783
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发表时间:
2012-10-15
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Holländer GA
Holländer GA
中科院分区:
其他
文献类型:
--
作者:
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

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Thymic epithelial cells provide unique cues for the life-long selection and differentiation of a repertoire of functionally diverse T cells. Rendered miRNA deficient, these stromal cells in the mouse lose their capacity to instruct the commitment of haematopoietic 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 antigen expression to prompt central immunological tolerance.
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