The Role of Tufts Cells in Salivary Gland Immunity

簇细胞在唾液腺免疫中的作用

基本信息

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
项目类别：
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&apos 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

项目摘要

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.

项目概要簇状细胞是罕见的胆碱能化学感应上皮细胞，能够产生一系列不寻常的化学反应。生物效应分子，如白细胞介素、类二十烷酸和神经递质。研究表明，簇细胞能够触发不同器官（例如肠道和呼吸道）的免疫反应通过 G 蛋白偶联受体依赖性途径，涉及化学感应转导的成分。尽管在唾液腺中检测到簇细胞，但它们在该器官中的功能尚不清楚。该项目旨在利用现代技术探索唾液腺上皮中的簇细胞生物学以及它们在先天性和适应性免疫中的作用。K99 阶段建议 (1) 研究簇细胞。通过先进的显微技术以及体内研究唾液腺上皮的分布和功能实验；（2）利用单细胞测定唾液腺上皮中的簇细胞化学感应成分分析；（3）利用体内簇细胞消融确定簇细胞对唾液腺先天免疫的影响在此期间，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以下课程独立的R00阶段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进行适应性免疫。生成的信息将有助于更好地了解唾液腺中的簇细胞生物学，并允许治疗唾液腺疾病的目标。