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: 10614064
• 负责人: Robert F. Margolskee
• 金额: $ 51.99万
• 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/10614064
• 关键词: Adult; Affect; Age; Air; Alveolar Bone Loss; Anti-Bacterial Agents; Atherosclerosis; Bacteria; Bacterial Infections; Cells; Cycloheximide; Cytoprotection; Dendritic Cells; Diabetes Mellitus; Disease; Elderly; Elements; Epithelial Attachment; Epithelium; Gene Expression; Gingiva; Goals; Grant; Growth; Health; Heterogeneity; Homeostasis; Immune; Immunity; Immunohistochemistry; Impairment; In Situ Hybridization; In Vitro; Inflammation; Inflammatory; Innate Immune Response; Knock-out; Knockout Mice; Lactones; Ligands; Liquid substance; Lymphoid Cell; Macrophage; Mediator; Microbe; Mucous Membrane; Mus; Natural Immunity; Oral; Oral health; Pathway interactions; Periodontal Diseases; Periodontitis; Population; Receptor Cell; Research; Rheumatoid Arthritis; Risk; Risk Factors; Role; Science; Sensory; Sentinel; Signal Pathway; Signal Transduction; Signaling Molecule; Systemic disease; Taste Buds; Taste Perception; Testing; Tissues; Tooth Loss; Tooth structure; Topical application; Wild Type Mouse; Work; alveolar bone; alveolar destruction; antimicrobial peptide; bone; bone loss; chemokine; cytokine; disability; dysbiosis; experimental study; homoserine lactone; knockout gene; microbial; microbiome composition; mouse model; novel strategies; oral bacteria; oral microbial community; oral microbiome; pathogen; prevent; protective effect; quorum sensing; receptor; response; selective expression; taste transduction; transcriptomics

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 牙周疾病是由细菌感染以及牙龈和骨骼感染引起的 环绕并支撑牙齿，几乎影响了30岁以上的美国成年人，其中约9％患有严重的牙周炎。 牙周炎的标志是破坏牙槽骨，最终导致牙齿脱落和口服 残疾。牙周炎是一个主要的口腔健康问题，尤其是在老年人中，这增加了 全身性疾病，包括动脉粥样硬化，类风湿关节炎和糖尿病。一般目标 该赠款是为了确定新发现的牙龈固体化学感应细胞（GSCC）在 防止牙周炎，以识别接收器，信号通路和先天涉及的影响 GSCC激活引起的免疫力，并识别激活GSCC的化合物以利用先天性 减少牙周炎的免疫力。 牙周炎是由多生物性营养不良的引起的，该牙周病疾病会使口服生态平衡 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。尽管对微生物和宿主免疫学如何对牙周炎有贡献知之甚少，但它是 仍不清楚哪种牙龈细胞可以预防该疾病。最近在几种类型的粘膜的研究中 鉴定出味觉细胞状的SCC是一种专门的化学敏感哨兵细胞，可检测细菌并引起宿主 先天免疫反应。 最近，我们已经在鼠标牙龈连接上皮中确定了GSCC，这是 上皮屏障可防止牙齿和周围牙龈的细菌感染。 GSCCS Express 苦味受体以及其他味道转移成分，对细菌信号分子做出反应， 并引发内在的先天免疫力以防止牙周炎。该提案的实验研究 GSCC在牙龈/牙齿健康中的作用以确定GSCC是否引起先天免疫调查 牙龈粘膜中口服细菌的过度生长（AIM 1）；确定接收器和信号成分 GSCC和GSCC促进牙龈释放抗菌胡椒的机制和 炎性细胞因子（AIM 2）；并确定GSCC信号通路的“按需”激活 减少牙周炎（AIM 3）。了解这些的启动接收器和基本机制 反应可能会导致促进口腔健康和治疗牙周炎的新方法。

项目成果

Oral Microbiota-Host Interaction Mediated by Taste Receptors.

味觉感受器介导的口腔微生物群与宿主的相互作用

• DOI: 10.3389/fcimb.2022.802504
• 发表时间: 2022
• 期刊: Frontiers in cellular and infection microbiology
• 影响因子: 5.7

Mouse Mandibular Retromolar Taste Buds Associated With a Mucus Salivary Gland.

小鼠下颌磨牙后味蕾与粘液唾液腺相关。

• DOI: 10.1093/chemse/bjab019
• 发表时间: 2021
• 期刊: Chemical senses
• 影响因子: 3.5
• 作者: Nguyen,QuanT;BeckCoburn,GraceE;Valentino,Amber;Karabucak,Bekir;Tizzano,Marco
• 通讯作者: Tizzano,Marco