Opportunities for Dental Research in Salivary Gland Immunobiology at Stony Brook

 描述（由申请人提供）：适当的唾液腺功能对于维持口腔健康和生理健康至关重要。唾液的功能是润湿口腔组织，作为语言的辅助，作为对味觉重要的溶剂，以及作为吞咽食物重要的咀嚼润湿剂/润滑剂。唾液在宿主防御中也起重要作用，并且是上消化道先天宿主防御的主要贡献者。唾液腺是口腔粘膜免疫系统的主要组成部分，其赋予对口腔和粘膜获得性病原体的抗原特异性免疫。我们证明，唾液腺除了作为效应位点外，还可以作为粘膜诱导位点，并且唾液腺的抗原刺激足以在近端和远端诱导免疫。 粘膜部位以及全身部位。了解唾液腺的免疫生物学也是特别感兴趣的，因为它涉及到唾液腺的基因治疗和组织工程的快速发展的进展。通过体内基因转移“重新工程化”唾液腺，从而原位恢复体液分泌，并使唾液内分泌途径外化用于全身性基因治疗的能力，为更好地理解唾液腺免疫如何与转移基因的表达相互作用提供了额外的理由，特别是因为转移基因经常利用重组病毒载体表达。小鼠巨细胞病毒（MCMV）感染已成为研究唾液腺免疫的工具。此外，MCMV感染已经被用作人CMV感染的模型一段时间了。人类CMV感染是常见的，但不会导致免疫功能正常的健康成年人的重大疾病。然而，在免疫功能低下的患者（移植受体或艾滋病患者）中，CMV感染成为严重的并发症和死亡原因。因此，了解对MCMV感染的免疫应答可以更好地了解人类CMV感染的发病机制。此外，人类CMV可通过口腔和呼吸道分泌物以及性传播传播。这使得研究对MCMV的粘膜应答，特别是与人类感染相关的粘膜应答。在本提案中，我们将利用 MCMV模型扩展了我们唾液腺接种，特别是腮腺导管插入的“概念验证”，可能是粘膜疫苗的重要的新临床途径。这个项目非常适合短期夏季接触到“牙科学生”感兴趣的研究，可以很容易地在学年的过程中扩展。我们期望这些研究的结果将大大增加我们对唾液腺诱导的粘膜免疫的理解。该地区补助金的授予将通过培养奖学金和批判性思维能力，实现牙科医学院学生研究的目标， 增加科学知识的主体，并促进学生进入学术，牙科研究事业的招聘。

 DESCRIPTION (provided by applicant): Proper salivary gland function is critical for the maintenance of oral health and physiological well-being. Saliva functions to moisten the oral tissues as an aid for speech, as a solvent important for taste, and as a masticatory wetting agent/lubricant important in swallowing food. Saliva also plays an important role in host defense and is a major contributor of the innate host defense of the upper gastrointestinal tract. The salivary glands are a major component in the mucosal immune system of the oral cavity that confers antigen- specific immunity to oral and mucosally-acquired pathogens. We demonstrated that the salivary gland can act as a mucosal inductive site in addition to an effector site and tha antigenic stimulation of the salivary gland is sufficient to induce immunity at proximal and distal mucosal sites as well as systemic sites. Understanding the immunobiology of the salivary glands is also of particular interest because of rapidly developing progress in gene therapy and tissue engineering as it relates to the salivary gland. The ability to "re-engineer" the salivary gland via gene transfer in vivo with the resultant in situ restoration of fluid secretion and to utlize salivary endocrine secretory pathways for systemic gene therapeutics provides additional reason for gaining a better understanding of how salivary gland immunity interacts with the expression of transferred gene(s), especially because the transferred gene(s) are frequently expressed utilizing recombinant viral vectors. Murine cytomegalovirus (MCMV) infections have served as a tool for investigating salivary gland immunity. In addition, MCMV infections have already been used for some time as models for human CMV infection. Human CMV infections are common but do not lead to significant disease in immune-competent healthy adults. Nevertheless, in immune-compromised patients (transplant recipients or AIDS patients) CMV infection becomes a serious complication and source of mortality. Therefore, understanding the immune responses to MCMV infections can lead to a better understanding of the pathogenesis of CMV infections in humans. In addition, human CMV can be spread through oral and respiratory secretions and through sexual transmission. This makes investigating the mucosal responses to MCMV, in particular, relevant to infection in humans. In this proposal we will utilize the MCMV model to extend our "proof of concept" that salivary gland vaccination in particular cannulation of the parotid salivary gland, could be an important new clinical route for mucosal vaccines. This project is ideally suited for a short-term summer exposure to research of interest to the "dental student" that can easily be expanded over the course of the academic year. We expect that the outcomes of these studies will greatly add to our understanding of salivary gland induced mucosal immunity. The award of this AREA grant will meet the goals of student research at the School of Dental Medicine by fostering scholarship and critical thinking skills, by adding to the body of scientific knowledge, and by facilitating recruitment of students into academic, dental research careers.