The role of solitary chemosensory cells in periodontal homeostasis

项目摘要 牙周病，由细菌感染和牙龈和骨骼的炎症引起 在30岁以上的美国成年人中，近一半的人患有牙周炎，其中约9%患有严重的牙周炎。 牙周炎的特征是牙槽骨的破坏，最终导致牙齿的广泛脱落和口腔。 残疾。牙周炎是一种主要的口腔健康问题，尤其是在老年人中，它增加了患牙周炎的风险 系统性疾病，包括动脉粥样硬化、类风湿性关节炎和糖尿病。的总体目标 这项资助是为了确定新发现的牙龈孤立化学感觉细胞(GSCCs)在 预防牙周炎，确定先天参与的受体、信号通路和效应器 GSCC激活引起的免疫，并鉴定激活GSCC以利用宿主先天的化合物 免疫力，减少牙周炎。 牙周炎是由多种微生物引起的，它扰乱了口腔的生态平衡。 微生物区系，以及宿主先天免疫的破坏，这也有助于破坏 牙周组织。虽然关于微生物和宿主免疫是如何导致牙周炎的已知很多，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已经 发现味觉细胞样干细胞是检测细菌和唤起宿主的特殊化学敏感前哨细胞 先天免疫反应。 最近，我们在小鼠的牙龈连接上皮中发现了gscc，它是 上皮屏障，防止牙齿和周围牙龈的细菌感染。GSCCS快递 苦味感受器与其他味觉转导成分一起，对细菌信号分子做出反应， 并触发先天免疫，预防牙周炎。这一方案的实验研究了 GSCCs在牙龈/牙齿健康中的作用确定gSCCs是否能激发先天免疫反应，从而防止 口腔细菌在牙龈粘膜中过度生长(目标1)；确定口腔细菌的受体和信号成分 GSCCs及其促进牙周抗菌肽释放的机制 炎性细胞因子(目标2)；并确定GSCC信号通路是否按需激活 减少牙周炎(目标3)。了解它们的启动受体和潜在机制 这些反应可能会带来促进口腔健康和治疗牙周炎的新方法。

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.