Exploring roles of protein deamidation in oral inflammation

摘要 炎症是身体对物理损伤或病原体感染引起的损伤的反应。口腔 腔、胃肠道、皮肤、肺和泌尿生殖道代表了宿主细胞 与各种微生物广泛接触，为感染和炎症提供了充足的机会。 最近的进展已经揭示了微生物群的关键作用，主要来自肠道，在人类健康和 疾病我们对其他部位，特别是口腔的粘膜免疫的理解是非常重要的。 有限公司除了微生物组之外，病毒如何导致口腔炎症及其疾病 仍然未知。 新兴的临床研究表明，人类疱疹病毒（例如，EB病毒和巨细胞病毒） 在患有严重炎性疾病的患者的口腔中经常检测到， 牙周炎、种植体周围炎和粘膜炎。其他研究也表明，炎症可以促进 疱疹病毒在口腔中的再活化和复制。然而，疱疹病毒如何有助于口腔 炎症和潜在的分子机制从未被探索过。建立在我们最近的 发现疱疹病毒部署蛋白脱酰胺操纵宿主免疫反应，这项研究将 通过回答以下问题的研究直接解决上述知识差距：1） 口腔炎症性疾病中疱疹病毒感染; 2）核酸传感途径如何在口腔炎症性疾病中运作 免疫防御和影响口腔炎性疾病; 3）疱疹病毒如何逃避核酸- 感测通路冲击口腔炎症; 4）蛋白质脱酰胺在病毒感染中的调节作用是什么？ 口腔中的感染和免疫防御;以及5）我们能否利用蛋白质脱酰胺来驯服口腔 炎症和治疗口腔炎性疾病。这项工作将阐明的作用和分子基础， 先天免疫感应、疱疹病毒感染和口腔炎症中的蛋白质脱酰胺。利用我们 了解蛋白质脱酰胺的相关知识，我们将开发用于纠正慢性炎症和治疗口腔疾病的关键试剂。 炎症性疾病。

Abstract Inflammation is the body's response to damage induced by physical injury or pathogen infection. The oral cavity, gastrointestinal track, skin, lung and urogenital track represent distinct anatomical sites where host cells interface extensively with diverse microbes, presenting ample opportunities for infection and inflammation. Recent advances have uncovered pivotal roles of microbiota, primarily from the gut, in human health and disease. Our understanding in mucosal immunity of the other sites, particularly the oral cavity, is extremely limited. How viruses, in addition to the microbiome, contribute to oral inflammation and diseases thereof remains unknown. Emerging clinical studies revealed that human herpesviruses (e.g., Epstein-Barr virus and cytomegalovirus) were frequently detected in the oral cavity of patients with severe forms of inflammatory diseases, such as periodontitis, peri-implantitis and mucositis. Other studies also suggest that inflammation can promote herpesvirus reactivation and replication in the oral cavity. However, how herpesviruses contribute to oral inflammation and the underlying molecular mechanisms have never been explored. Built on our recent discovery that herpesviruses deploy protein deamidation to manipulate host immune response, this study will directly address the above knowledge gap with research answering the following questions: 1) What is the role of herpesvirus infection in oral inflammatory diseases; 2) How do nucleic acid sensing pathways operate in oral immune defense and impact oral inflammatory disease; 3) How does herpesviral evasion of nucleic acid- sensing pathways impinge on oral inflammation; 4) What are the regulatory role of protein deamidation in viral infection and immune defense in the oral cavity; and 5) Can we leverage protein deamidation to tame oral inflammation and treat oral inflammatory diseases. This work will illuminate the role and molecular basis of innate immune sensing, herpesvirus infection and protein deamidation in oral inflammation. Harnessing our knowledge of protein deamidation, we will develop key reagents to rectify chronic inflammation and treat oral inflammatory diseases.