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Critical role for miR-181a/b-1 in agonist selection of invariant natural killer T cells.


ABSTRACT: T-cell receptor (TCR) signal strength determines selection and lineage fate at the CD4(+)CD8(+) double-positive stage of intrathymic T-cell development. Members of the miR-181 family constitute the most abundantly expressed microRNA at this stage of T-cell development. Here we show that deletion of miR-181a/b-1 reduced the responsiveness of double-positive thymocytes to TCR signals and virtually abrogated early invariant natural killer T (iNKT) cell development, resulting in a dramatic reduction in iNKT cell numbers in thymus as well as in the periphery. Increased concentrations of agonist ligand rescued iNKT cell development in miR-181a/b-1(-/-) mice. Our results define a critical role of miR-181a/b-1 in early iNKT cell development and show that miR-181a/b-1 sets a TCR signaling threshold for agonist selection.

SUBMITTER: Zietara N 

PROVIDER: S-EPMC3645533 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Critical role for miR-181a/b-1 in agonist selection of invariant natural killer T cells.

Ziętara Natalia N   Łyszkiewicz Marcin M   Witzlau Katrin K   Naumann Ronald R   Hurwitz Robert R   Langemeier Jörg J   Bohne Jens J   Sandrock Inga I   Ballmaier Matthias M   Weiss Siegfried S   Prinz Immo I   Krueger Andreas A  

Proceedings of the National Academy of Sciences of the United States of America 20130415 18


T-cell receptor (TCR) signal strength determines selection and lineage fate at the CD4(+)CD8(+) double-positive stage of intrathymic T-cell development. Members of the miR-181 family constitute the most abundantly expressed microRNA at this stage of T-cell development. Here we show that deletion of miR-181a/b-1 reduced the responsiveness of double-positive thymocytes to TCR signals and virtually abrogated early invariant natural killer T (iNKT) cell development, resulting in a dramatic reduction  ...[more]

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