Characterizing the role of viral microRNAs in regulating macrophage plasticity

病毒microRNAs在调节巨噬细胞可塑性中的作用 Afsar Raza Naqvi博士 越来越多的证据表明人类疱疹病毒(HHV)感染与口腔炎症性疾病有关。 这些病毒建立了终生感染，需要免疫逃避。像真核生物一样，HHV编码 MicroRNAs(MiRNA)是一种非蛋白质编码的调节RNA。MiRNAs与靶基因结合并沉默 表达从而控制包括细胞分化、凋亡、免疫在内的各种生物学过程 病毒miRNAs(VmiRs)在发病机制中起关键作用，因为它们可以调节两者的表达 病毒和宿主衍生的转录本。在我们的初步研究中，我们发现了几种vmiR的诱导水平 牙髓发炎或牙周病患者的活检。巨噬细胞(Mφ)是巨噬细胞的重要组成部分 口腔黏膜的免疫监测。根据激活状态，Mφ被归类为经典 促炎症(M1)和替代抗炎(M2)。我们的目标是描述我们以前的角色 确定了通过调节宿主φ可塑性来调节M miR可塑性的候选vmiRs。Vmir的影响 将评估M1和M2 Mφ介导的细胞和外体miRNAi的差异表达。 Vmir介导的Mφ可塑性的功能调节将通过检测相关的表型来评估 记号笔。这方面以前没有研究过，可能会对vmir的作用提供新的见解。 在口腔疾病的发病机制中起重要作用。髓系细胞与周围口腔角质形成细胞的动态相互作用 是放大先天免疫反应以获得有利结果所必需的。来源的外切体的作用 表达M1和M2 Mφ的vmir将被检测在原发人类口腔的关键生物学功能上 角质形成细胞包括天然免疫反应、细胞增殖和迁移。生成的数据将 提供重要信息以弥补现有的知识差距。重要的是，因为vmiR不是内源性的 RNA，它们有可能被部署为潜在的治疗靶点。

Characterizing the role of viral microRNAs in regulating macrophage plasticity Afsar Raza Naqvi, Ph.D. Emerging evidences show implication of human herpesviruses (HHV) infection in oral inflammatory diseases. These viruses establish lifelong infection which requires immune evasion. HHV, like eukaryotes, encode microRNAs (miRNA) which are non-protein coding regulatory RNAs. MiRNAs binds to and silence target gene expression thereby controlling various biological processes including cell differentiation, apoptosis, immune responses, etc. Viral miRNAs (vmiRs) play critical role in pathogenesis as they can regulate expression of both virus and host derived transcripts. In our preliminary studies, we identified induced levels of several vmiRs in biopsies from patients with inflamed pulps or diseased gingiva. Macrophages (Mφ) are important component of immune surveillance in oral mucosa. Depending on the activation status, Mφ are categorized as classical proinflammatory (M1) and alternative antiinflammatory (M2). We aim to characterize the role of our previously identified candidate vmiRs in regulating Mφ plasticity through modulation of host miRNAs. The impact of vmiR mediated differential expression of cellular and exosomal miRNA profiles of M1 and M2 Mφ will be assessed. VmiR mediated functional modulation of Mφ plasticity will be assessed by examining phenotype associated markers. This aspect has not been investigated earlier and will likely provide novel insights on the role of vmiR in the pathogenesis of oral diseases. Dynamic interaction of myeloid cells with surrounding oral keratinocytes is required to amplify innate immune responses for a favorable outcome. The effect of exosomes derived from vmiR expressing M1 and M2 Mφ will be examined on key biological functions of primary human oral keratinocytes including innate immune responses, cell proliferation and migration. The data generated will provide significant information to address existing knowledge gaps. Importantly, as vmiRs are not endogenous RNAs, they have the potential to be deployed as potential therapeutic targets.