The Role of Tufts Cells in Salivary Gland Immunity

簇细胞在唾液腺免疫中的作用

• 批准号: 10738663
• 负责人: Harim Tavares Dos Santos
• 金额: $ 10.1万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-18 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10738663
• 关键词: Ablation; Affect; Area; Autoimmune Diseases; Binding; Biological; Cell Lineage; Cell physiology; Cells; Cellular Structures; Cellular biology; Chronic; Coupled; Detection; Development; Disease; Dryness; Eicosanoids; Electron Microscopy; Epithelial Cells; Epithelium; Exhibits; Exocrine Glands; Exposure to; Family; Follow-Up Studies; Foundations; G-Protein-Coupled Receptors; Generations; Genes; Helper-Inducer T-Lymphocyte; Homeobox; Host Defense; Human; IL17 gene; Immune; Immune response; Immune signaling; Immunity; Impairment; Inflammation; Inflammatory; Innate Immune Response; Interleukin-13; Interleukin-4; Interleukin-5; Interleukins; Intestines; Investigation; Laboratories; Lipopolysaccharides; Literature; Lymphocytic Infiltrate; Mediating; Mentors; Mentorship; Microscopic; Microscopy; Minor salivary gland structure; Modernization; Molecular Biology; Molecular Immunology; Mus; Natural Immunity; Neurotransmitters; Oral cavity; Organ; Pathogenesis; Pathway interactions; Patients; Phase; Phospholipase; Play; Principal Investigator; Production; Proteins; Rattus; Receptor Signaling; Research; Research Personnel; Resolution; Role; Saliva; Salivary Gland Diseases; Salivary Glands; Sensory; Shapes; Signal Transduction; Sjogren' s Syndrome; Source; Specimen; Structure; Submandibular gland; TRPM5 gene; Taste Buds; Techniques; Technology; Time; Tissues; Training; Work; adaptive immune response; adaptive immunity; airway epithelium; alpha-gustducin; cell type; cellular microvillus; cholinergic; cytokine; defense response; design; experimental study; follow-up; gastrointestinal epithelium; immune function; immune system function; immunoregulation; in vivo; in vivo Model; innate immune function; insight; interleukin-17E; member; mouse model; neutralizing antibody; novel; pathogen; programs; receptor; receptor-mediated signaling; response; single cell analysis; single-cell RNA sequencing; therapeutic target; transcription factor; transcriptomics

PROJECT SUMMARY Tuft cells are rare cholinergic chemosensory epithelial cells capable of producing an unusual spectrum of biological effector molecules, such as interleukins, eicosanoids and neurotransmitters. Previous studies have shown that tuft cells are capable of triggering immune responses in different organs (e.g., intestine and airways) via G protein-coupled receptor-dependent pathways, involving components of chemosensory transduction. Although tuft cells have been detected in salivary glands, their functions in this organ are unknown. The aims of this project are designed to utilize modern technologies to explore tuft cells biology in salivary gland epithelium as well as their role in innate and adaptive immunity. The K99 phase proposes to (1) to investigate tuft cell distribution and function in salivary gland epithelium through advanced microscopic techniques as well as in vivo experiments; (2) to determine tuft cell chemosensory components in salivary gland epithelium using single cell analysis; (3) to determine the effects of tuft cell on salivary gland innate immunity using tuft cell ablation in vivo model. During this time the candidate will complete mentored training in molecular immunology and biology, high-resolution microscopy, single cell RNA sequencing and spatial transcriptomics as well as courses in professional development. The independent R00 phase will investigate the role of tuft cells in salivary gland adaptive immunity utilizing Sjögren’s syndrome-like mouse models and human specimens. Together, the new generated information will allow a better understanding of tuft cell biology in salivary gland and allow therapeutic targets for salivary gland diseases.

项目摘要 簇状细胞是一种罕见的胆碱能化学感觉上皮细胞，能够产生一种不寻常的谱， 生物效应分子，如白细胞介素、类花生酸和神经递质。先前的研究 显示簇状细胞能够触发不同器官中的免疫应答（例如，肠和气道） 通过G蛋白偶联受体依赖性途径，涉及化学感受性转导的组分。 虽然在唾液腺中发现了簇状细胞，但它们在该器官中的功能尚不清楚。的目的 本项目旨在利用现代技术探索唾液腺上皮中的簇状细胞生物学 以及它们在先天性和适应性免疫中的作用。K99阶段提出（1）研究簇状细胞 通过先进的显微技术以及体内研究， 实验;（2）用单细胞免疫荧光法测定唾液腺上皮中簇状细胞化学感受成分 （3）通过在体去除簇状细胞（tuftcellablation）的方法，观察簇状细胞对唾液腺天然免疫功能的影响 模型在此期间，候选人将完成分子免疫学和生物学方面的指导培训， 高分辨率显微镜，单细胞RNA测序和空间转录组学以及课程， 专业发展。独立的R 00期将研究簇状细胞在唾液腺中的作用 利用干燥综合征样小鼠模型和人类标本的适应性免疫。在一起，新 所产生的信息将允许更好地理解唾液腺中的簇状细胞生物学，并允许治疗。 唾液腺疾病的靶点。