Dai Rujuan, Ahmed S Ansar
Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA.
Ther Clin Risk Manag. 2014 Mar 3;10:151-63. doi: 10.2147/TCRM.S33517. eCollection 2014.
Autoimmune diseases encompass a diverse group of diseases which emanate from a dysregulated immune system that launches a damaging attack on its own tissues. Autoimmune attacks on self tissues can occur in any organ or body system. A notable feature of autoimmune disease is that a majority of these disorders occur predominantly in females. The precise basis of sex bias in autoimmune diseases is complex and potentially involves sex chromosomes, sex hormones, and sex-specific gene regulation in response to internal and external stimuli. Epigenetic regulation of genes, especially by microRNAs (miRNAs), is now attracting significant attention. miRNAs are small, non-protein-coding RNAs that are predicted to regulate a majority of human genes, including those involved in immune regulation. Therefore, it is not surprising that dysregulated miRNAs are evident in many diseases, including autoimmune diseases. Because there are marked sex differences in the incidence of autoimmune diseases, this review focuses on the role of sex factors on miRNA expression in the context of autoimmune diseases, an aspect not addressed thus far. Here, we initially review miRNA biogenesis and miRNA regulation of immunity and autoimmunity. We then summarize the recent findings of sexual dimorphism of miRNA expression in diverse tissues, which imply a critical role of miRNA in sex differentiation and in sex-specific regulation of tissue development and/or function. We also discuss the important contribution of the X chromosome and sex hormones to the sexual dimorphism of miRNA expression. Understanding sexually dimorphic miRNA expression in sex-biased autoimmune diseases not only offers us new insight into the mechanism of sex bias of the disease but will also aid us in developing new sex-based therapeutic strategies for the efficient treatment of these diseases with a sex bias.
自身免疫性疾病包括多种疾病，这些疾病源于免疫系统失调，对自身组织发动破坏性攻击。对自身组织的自身免疫攻击可发生在任何器官或身体系统。自身免疫性疾病的一个显著特征是，这些疾病中的大多数主要发生在女性身上。自身免疫性疾病中性别偏向的确切基础很复杂，可能涉及性染色体、性激素以及对内部和外部刺激作出反应的性别特异性基因调控。基因的表观遗传调控，尤其是微小RNA（miRNA）的调控，目前正受到广泛关注。miRNA是小的非蛋白质编码RNA，预计可调控大多数人类基因，包括那些参与免疫调节的基因。因此，miRNA失调在包括自身免疫性疾病在内的许多疾病中很明显也就不足为奇了。由于自身免疫性疾病的发病率存在明显的性别差异，本综述重点关注性别因素在自身免疫性疾病背景下对miRNA表达的作用，这是一个迄今为止尚未涉及的方面。在这里，我们首先综述miRNA的生物合成以及miRNA对免疫和自身免疫的调控。然后，我们总结了不同组织中miRNA表达性别差异的最新研究结果，这意味着miRNA在性别分化以及组织发育和/或功能的性别特异性调控中起着关键作用。我们还讨论了X染色体和性激素对miRNA表达性别差异的重要贡献。了解性别偏向的自身免疫性疾病中性别差异的miRNA表达，不仅能让我们对该疾病的性别偏向机制有新的认识，还将有助于我们开发基于性别的新治疗策略，以有效治疗这些有性别偏向的疾病。
