Critical role for miR-181a/b-1 in agonist selection of invariant natural killer T cells
Critical role for miR-181a/b-1 in agonist selection of invariant natural killer T cells
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DOI：
10.1073/pnas.1221984110
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发表时间：
2013-04
期刊：
影响因子：
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通讯作者：
Natalia Ziętara;Marcin Łyszkiewicz;Katrin Witzlau;R. Naumann;R. Hurwitz;Jörg Langemeier;J. Bohne;I. Sandrock;M. Ballmaier;S. Weiss;I. Prinz;A. Krueger
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文献类型：
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作者：
Natalia Ziętara;Marcin Łyszkiewicz;Katrin Witzlau;R. Naumann;R. Hurwitz;Jörg Langemeier;J. Bohne;I. Sandrock;M. Ballmaier;S. Weiss;I. Prinz;A. Krueger
T 细胞受体 (TCR) 信号强度决定胸腺内 T 细胞发育的 CD4+CD8+ 双阳性阶段的选择和谱系命运。 miR-181 家族的成员构成了 T 细胞发育这一阶段表达最丰富的 microRNA。在这里，我们发现，miR-181a/b-1的缺失降低了双阳性胸腺细胞对TCR信号的反应性，并实际上消除了早期不变自然杀伤T（iNKT）细胞的发育，导致胸腺和外周iNKT细胞数量急剧减少。增加激动剂配体浓度可以挽救 miR-181a/b-1−/− 小鼠中的 iNKT 细胞发育。我们的结果定义了 miR-181a/b-1 在早期 iNKT 细胞发育中的关键作用，并表明 miR-181a/b-1 为激动剂选择设定了 TCR 信号阈值。
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.