The role of solitary chemosensory cells in periodontal homeostasis

孤立化学感应细胞在牙周稳态中的作用

• 批准号: 10542979
• 负责人: Robert F. Margolskee
• 金额: $ 32.65万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10542979
• 关键词: role; solitary; chemosensory; cells; periodontal

Project Summary Periodontal disease, which results from bacterial infection and inflammation of the gums and bone that surround and support the teeth, affects nearly half of US adults over 30, with ~9% having severe periodontitis. The hallmark of periodontitis is destruction of alveolar bone, resulting ultimately in extended tooth loss and oral disability. Periodontitis is a major oral health problem, particularly among the elderly, that increases the risk for systemic diseases, including atherosclerosis, rheumatoid arthritis, and diabetes mellitus. The general goals of this grant are to determine the role of newly discovered gingival solitary chemosensory cells (gSCCs) in protecting against periodontitis, to identify the receptors, signaling pathways and effectors involved in innate immunity evoked by gSCC activation, and to identify compounds that activate gSCCs to harness host innate immunity to reduce periodontitis. Periodontitis results from polymicrobial dysbiosis, which perturbs the ecologically balanced oral microbiota, and from disruption of the host innate immunity, which also contributes to the destruction of periodontal tissue. While much is known about how microbes and host immunity contribute to periodontitis, it is still unclear which gingival cells protect against the disease. Recent studies in several types of mucosae have identified taste cell-like SCCs as specialized chemosensitive sentinel cells that detect bacteria and evoke host innate immune responses. Most recently, we have identified gSCCs in the mouse gingival junctional epithelium that is part of the epithelial barrier protecting against bacterial infection of the tooth and surrounding gingiva. gSCCs express bitter taste receptors along with other taste transduction components, respond to bacterial signaling molecules, and trigger intrinsic innate immunity to protect against periodontitis. The experiments of this proposal study the role of gSCCs in gingival/tooth health to determine if gSCCs evoke innate immune responses that prevent overgrowth of oral bacteria in the gingival mucosa (Aim 1); identify the receptors and signaling components of gSCCs and the mechanism by which gSCCs promote gingival release of antimicrobial peptides and inflammatory cytokines (Aim 2); and determine if “on demand “activation of the gSCC signaling pathway reduces periodontitis (Aim 3). Understanding the initiating receptors and underlying mechanisms of these responses may lead to new approaches to promote oral health and treat periodontitis.

项目摘要 牙周病，由细菌感染和牙龈和骨骼炎症引起， 牙周炎是一种围绕和支撑牙齿的疾病，影响了近一半的30岁以上的美国成年人，其中约9%患有严重的牙周炎。 牙周炎的标志是牙槽骨的破坏，最终导致牙齿脱落和口腔溃疡。 残疾。牙周炎是一个主要的口腔健康问题，特别是在老年人中， 全身性疾病，包括动脉粥样硬化、类风湿性关节炎和糖尿病。的总目标 这项资助旨在确定新发现的牙龈孤立化学感受细胞（gSCC）在 预防牙周炎，以确定参与先天性牙周炎的受体、信号通路和效应子。 本发明涉及由gSCC激活诱发的免疫的方法，并鉴定激活gSCC以利用宿主先天性免疫的化合物。 免疫力降低牙周炎。 牙周炎是由多种微生物的生态失调引起的， 微生物群，以及宿主先天免疫的破坏，这也有助于破坏 牙周组织虽然我们对微生物和宿主免疫力如何导致牙周炎了解很多，但 目前还不清楚哪些牙龈细胞可以预防这种疾病。最近对几种类型的粘膜的研究 鉴定出味细胞样SCC作为检测细菌和诱发宿主的特化化学敏感性哨兵细胞， 先天免疫反应 最近，我们已经在小鼠牙龈结合上皮中鉴定出gSCC， 保护牙齿和周围牙龈免受细菌感染的上皮屏障。gSCC表达 苦味受体沿着其它味觉传导组分，响应细菌信号分子， 并触发固有的先天免疫以防止牙周炎。该方案的实验研究了 gSCC在牙龈/牙齿健康中的作用，以确定gSCC是否引起先天免疫应答， 牙龈粘膜中口腔细菌的过度生长（目标1）;识别 gSCC和gSCC促进抗菌肽的牙龈释放的机制， 炎性细胞因子（目的2）;并确定是否“按需“激活gSCC信号通路 减少牙周炎（目标3）。了解这些的起始受体和潜在机制 这些反应可能导致促进口腔健康和治疗牙周炎的新方法。