Opportunities for Dental Research in Salivary Gland Immunobiology at Stony Brook

石溪分校唾液腺免疫生物学牙科研究机会

• 批准号: 8865822
• 负责人: STEVEN D LONDON
• 金额: $ 42.23万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-03-10 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8865822
• 关键词: Academic Research Enhancement Awards; Acquired Immunodeficiency Syndrome; Address; Adult; Antibodies; Antigens; Applications Grants; Award; B-Lymphocytes; Bacteria; Body Surface; Cannulations; Cells; Characteristics; Clinical; Complication; Critical Thinking; Cytomegalovirus; Cytomegalovirus Infections; Data; Defense Mechanisms; Deglutition; Dental Research; Dental Schools; Dental Students; Disease; Distal; Endocrine; Engineering; Environment; Epithelium; Exocrine Glands; Exposure to; Fluids and Secretions; Follicular Dendritic Cells; Food; Fostering; Funding; Gene Transfer; Goals; Grant; Gut associated lymphoid tissue; Host Defense; Human; Immune; Immune response; Immune system; Immunity; Immunization; Immunobiology; Immunoglobulin A; Immunoglobulin Class Switching; In Situ; Infection; Ingestion; Injection of therapeutic agent; Institution; Knowledge; Lamina Propria; Lead; Lubricants; Lymphocyte; Lymphoid; Lymphoid Tissue; M cell; Maintenance; Medicine; Modeling; Mucosal Immune Responses; Mucosal Immunity; Mucous Membrane; Murid herpesvirus 1; Nose; Oral; Oral cavity; Oral health; Oral mucous membrane structure; Outcome; Outcome Study; Parotid Gland; Pathogenesis; Pathway interactions; Patients; Personal Satisfaction; Physiological; Play; Population; Process; Proliferating; Public Health; Research; Role; Route; Saliva; Salivary; Salivary Glands; Scholarship; Schools; Sexual Transmission; Site; Solvents; Source; Speech; Structure of germinal center of lymph node; Students; Surface; T-Lymphocyte; Taste Perception; Techniques; Time; Tissue Engineering; Tissues; Transplant Recipients; Universities; Upper digestive tract structure; Upper respiratory tract; Vaccination; Vaccines; Virus; Wetting Agents; burden of illness; career; enhancing factor; gene therapy; immunopathology; in vivo; interest; lymph nodes; meetings; mortality; mucosal site; mucosal vaccine; oral tissue; pathogen; plasma cell differentiation; programs; public health relevance; recombinant viral vector; respiratory; response; restoration; saliva function; skills; therapeutic gene; tissue culture; tool; vaccine development

 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.

 描述(申请人提供)：适当的唾液腺功能对维持口腔健康和生理健康至关重要。唾液的功能是滋润口腔组织，作为说话的辅助工具，作为味觉的重要溶剂，以及吞咽食物时的咀嚼润湿剂/润滑剂。唾液也在宿主防御中发挥重要作用，是上胃肠道天然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，为口腔和粘膜获得性病原体提供抗原特异性免疫。我们证明，唾液腺除了作为效应部位外，还可以作为粘膜诱导部位，唾液腺的抗原刺激足以在近端和远端诱导免疫。 粘膜部位和全身部位。由于与唾液腺相关的基因治疗和组织工程的快速发展，了解唾液腺的免疫生物学也特别有趣。通过体内基因转移“重新设计”唾液腺，从而原位恢复液体分泌，并将唾液内分泌途径用于系统基因治疗，这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(S)，特别是因为转移基因(S)经常利用重组病毒载体表达。小鼠巨细胞病毒(MCMV)感染已被用作研究唾液腺免疫的工具。此外，MCMV感染已经被用作人类CMV感染的模型已经有一段时间了。人类巨细胞病毒感染很常见，但在具有免疫能力的健康成年人中不会导致重大疾病。然而，在免疫功能低下的患者(移植受者或艾滋病患者)中，CMV感染成为一种严重的并发症和死亡来源。因此，了解巨细胞病毒感染的免疫应答有助于更好地了解人类巨细胞病毒感染的发病机制。此外，人类巨细胞病毒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的粘膜反应，特别是与人类感染有关。在这份提案中，我们将利用 MCMV模型扩展了我们关于唾液腺疫苗接种，特别是腮腺插管接种的“概念证明”，可能是黏膜疫苗的一条重要的新临床路线。这个项目非常适合暑期短期接触“牙科学生”感兴趣的研究，这些研究可以很容易地在一学年的课程中扩展。我们期望这些研究的结果将极大地增加我们对唾液腺诱导的粘膜免疫的理解。这一领域的拨款将通过培养奖学金和批判性思维技能来满足牙医学院学生研究的目标，通过 增加科学知识的主体，并促进学生进入学术和牙科研究职业。