MicroRNA-181a/b-1 Is Not Required for Innate γδ NKT Effector Cell Development.
MicroRNA-181a/b-1 Is Not Required for Innate γδ NKT Effector Cell Development.
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DOI：
10.1371/journal.pone.0145010
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Prinz I
中科院分区：
文献类型：
--
作者：
Sandrock I;Ziętara N;Łyszkiewicz M;Oberdörfer L;Witzlau K;Krueger A;Prinz I
胸腺αβ T淋巴细胞发育为恒定的自然杀伤（NK）T细胞取决于它们通过CD 1d呈递的激动性脂质抗原的选择。如果成功，新选择的NKT细胞获得胸腺中已有的效应子功能。一些γδ T细胞亚群也在胸腺中获得效应子功能。然而，尚不清楚激动性TCR刺激是否参与胸腺γδ T细胞的选择和发育。在这里，我们结合联合收割机两个遗传模型来解决这个问题。MiR-181 a/B-1-/-小鼠显示对不变αβ NKT细胞的激动性T细胞选择受损，将其与Tcrd-H2 BeGFP报告小鼠杂交以监测γδ T细胞的选择、胸腺内扩增和分化。我们发现miR-181 a/B-1缺陷对胸腺γδ T细胞的数量或它们向产生IL-17或IFN-γ的效应表型的分化没有影响。外周淋巴结γδ T细胞的组成不受miR-181 a/B-1缺陷的影响。树突状表皮γδ T细胞通常存在于敲除动物中。然而，我们观察到肝脏中γδ NKT细胞的频率和数量增加，这可能是因为γδ NKT细胞可以扩增并取代外周小生境中缺失的αβ NKT细胞。总之，我们研究了miR-181 a/B-1对γδ T细胞的选择、胸腺内发育和稳态的作用。我们的结论是，T细胞选择的miR-181 a/B-1依赖性调节对于γδ NKT细胞或任何其他γδ T细胞亚型的先天发育不是关键性的。
Thymic development of αβ T lymphocytes into invariant natural killer (NK) T cells depends on their selection via agonistic lipid antigen presented by CD1d. If successful, newly selected NKT cells gain effector functions already in the thymus. Some γδ T cell subsets also acquire effector functions in the thymus. However, it is not clear whether agonistic TCR stimulation is involved in thymic γδ T cell selection and development. Here we combine two genetic models to address this question. MiR-181a/b-1–/–mice, which show impaired agonistic T cell selection of invariant αβ NKT cells, were crossed to Tcrd-H2BeGFP reporter mice to monitor selection, intra-thymic expansion and differentiation of γδ T cells. We found that miR-181a/b-1-deficiency had no effect on numbers of thymic γδ T cell or on their differentiation towards an IL-17- or IFN-γ-producing effector phenotype. Also, the composition of peripheral lymph node γδ T cells was not affected by miR-181a/b-1-deficiency. Dendritic epidermal γδ T cells were normally present in knock-out animals. However, we observed elevated frequencies and numbers of γδ NKT cells in the liver, possibly because γδ NKT cells can expand and replace missing αβ NKT cells in peripheral niches. In summary, we investigated the role of miR-181a/b-1 for selection, intrathymic development and homeostasis of γδ T cells. We conclude that miR-181a/b-1-dependent modulation of T cell selection is not critically required for innate development of γδ NKT cells or of any other γδ T cell subtypes.