1] Henry Ford Immunology Program, Henry Ford Hospital, Detroit, MI, USA [2] Department of Dermatology, Henry Ford Hospital, Detroit, MI, USA [3] Department of Internal Medicine, Henry Ford Hospital, Detroit, MI, USA.
1] Henry Ford Immunology Program, Henry Ford Hospital, Detroit, MI, USA [2] Department of Dermatology, Henry Ford Hospital, Detroit, MI, USA.
Genes Immun. 2014 Jan;15(1):57-61. doi: 10.1038/gene.2013.61. Epub 2013 Nov 28.
Langerhans cells (LCs) are bone marrow-derived immature skin-residential dendritic cells (DCs) with a life cycle distinct from that of other types of DCs. The mechanisms involved in LC homeostasis and immunological functions are still not clear. MicroRNAs (miRNAs) are a class of short noncoding RNAs that regulate gene expression through either translational repression or mRNA degradation. A recent study showed that specific deletion of total miRNAs in DCs affects the homeostasis and function of only LCs, but not of other types of DCs. The roles of specific individual miRNA in LC development are still lacking. The miRNA miR-17-92 class, encoding miR-17, miR-18, miR-19a, miR-19b, miR-20 and miR-92, plays a very important role in B- and T-cell development and function. Here, we first report that epidermal LCs highly express the miR-17-92 class compared with spleen naive T cells. To further characterize the role of miR-17-92 in LC development, we generated LC-specific miR-17-92 knockout and knock-in mice. Interestingly, LC-specific gain- and loss-of-function of miR-17-92 cluster did not significantly change LC homeostasis, maturation ability, antigen capture and migration to draining lymph nodes. Thus, the miR-17-92 cluster may be functionally redundant and not critically required for LC development and function.
朗格汉斯细胞(LCs)是骨髓来源的不成熟皮肤驻留树突状细胞(DCs),其生命周期与其他类型的 DCs 不同。LC 稳态和免疫功能的相关机制尚不清楚。微小 RNA(miRNAs)是一类短的非编码 RNA,通过翻译抑制或 mRNA 降解来调节基因表达。最近的一项研究表明,DC 中总 miRNAs 的特异性缺失仅影响 LCs 的稳态和功能,而不影响其他类型的 DCs。特定个体 miRNA 在 LC 发育中的作用仍不清楚。miR-17-92 类 miRNA 编码 miR-17、miR-18、miR-19a、miR-19b、miR-20 和 miR-92,在 B 细胞和 T 细胞发育和功能中起着非常重要的作用。在这里,我们首先报告表皮 LCs 比脾 naïve T 细胞高表达 miR-17-92 类。为了进一步研究 miR-17-92 在 LC 发育中的作用,我们生成了 LC 特异性 miR-17-92 敲除和敲入小鼠。有趣的是,LC 特异性获得和丧失 miR-17-92 簇的功能并没有显著改变 LC 的稳态、成熟能力、抗原捕获和迁移到引流淋巴结。因此,miR-17-92 簇可能具有功能冗余性,对 LC 的发育和功能不是必需的。