Microparticles Modulating Regulatory T cells in Periodontal Disease

微粒调节牙周病中的调节性 T 细胞

基本信息

批准号：
10285799
负责人：
Nisarg J. Shah
金额：
$ 14.35万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-01 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10285799
关键词：
Affect Animal Model Anti-Inflammatory Agents Antigens Applications Grants Attenuated Autoimmune Diseases Bacteria Biological Bone Tissue CD4 Positive T Lymphocytes Cells Characteristics Chemical Structure Chronic Cicatrix Clinical Connective Tissue Consult Data Development Disease Disease Progression Drug Delivery Systems Encapsulated Environment Exhibits Exposure to FOXP3 gene Fibrosis Fluorescence Gingiva Gingivitis Glycolates Helper-Inducer T-Lymphocyte Homeostasis Human IL2RA gene Immune Immune response Immunologic Memory Immunology Immunophenotyping In Vitro Infection Inflammation Inflammation Mediators Inflammatory Interferon Type II Interleukin-10 Interleukin-17 Kinetics Label Lead Lesion Mastication Measurement Measures Mediating Mediator of activation protein Methods Modeling Mus Needles Neutrophil Activation Neutrophil Infiltration Oral Oral mucous membrane structure Participant Pathogenesis Pathogenicity Pathway interactions Peptide Hydrolases Periodontal Diseases Periodontitis Phenotype Play Polymers Production Proteins RNA Recurrence Regulatory T-Lymphocyte Research Research Personnel Resolution Role Scientist Sirolimus Site Spectrum Analysis Stimulus T memory cell T-Lymphocyte T-Lymphocyte Subsets TNF gene Testing Tissue Engineering Tissues Tretinoin Tumor-infiltrating immune cells Up-Regulation Work alveolar bone base beta-Cyclodextrins bone controlled release copolymer cytokine dietary effector T cell experimental study immunoregulation in vivo inflammatory modulation neutrophil novel pre-clinical prevent release factor soft tissue

项目摘要

PROJECT SUMMARY Periodontal disease (PD) is chronic inflammatory disorder characterized by the infection of gingiva, connective tissue and alveolar bone. Dense immune cell infiltrates are characteristic in PD, of which T cells are key mediators of the host response and are significant participants in PD progression. Among the participating T cell subsets, regulatory T cells (Treg) have been identified in PD-affected tissue and generally function to suppress pro-inflammatory T cells. However, in chronic inflammatory lesions, Treg may lose immunoregulatory function and, instead, produce pro-inflammatory cytokines. We hypothesize that restoring Treg function will influence the immune response in PD. To test the hypothesis, the project will develop immunomodulatory microparticles to functionally stabilize Treg in periodontal tissue. The project comprises two aims – Aim 1 will optimize the synthesis of biodegradable microparticles for encapsulating immunomodulatory factors. We will measure and tune the rate of release to sustain biologically relevant concentrations for mediating immunomodulation. By measuring in vitro immunophenotypic stability and cytokine production by Treg, we will assess bioactivity of the released factors. Aim 2 will test microparticle delivery in a mouse periodontitis model. We will measure in vivo degradation and quantify the local enhancement of Treg mediated by the microparticles. We will conduct functional measurements by measuring the concentrations of associated cytokines and tissue inflammation using histomorphometry-based analysis. Overall, the experiments will evaluate the feasibility of in vivo Treg expansion and stabilization for attenuating inflammation in PD. The PI is a New Investigator with expertise in drug delivery, tissue engineering and immunology and will collaborate with the co-I, a clinician-scientist with expertise in autoimmune disease with a focus on how inflammation-induced Treg instability results in pathogenic production of inflammatory cytokines. The results from the project will assess the feasibility of microparticle-mediated modulation of inflammatory T cells in PD and lead to a R01 grant application to comprehensively characterize immunomodulation for durably controlling chronic inflammation in PD.

项目摘要牙周疾病（PD）是慢性炎症性疾病，其特征是牙龈感染，结缔组织组织和牙槽骨。致密的免疫细胞浸润是PD的特征，其中T细胞是关键宿主反应的介体是PD进展的重要参与者。在参与的t中细胞子集，调节性T细胞（TREG）已在受PD影响的组织中鉴定出来，通常起作用抑制促炎性T细胞。但是，在慢性炎症病变中，Treg可能会失去免疫调节功能，而是产生促炎性细胞因子。我们假设还原treg功能将影响PD的免疫反应。为了检验该假设，该项目将开发免疫调节性微粒在功能上稳定牙周组织中的Treg。该项目包括两个目标 - 目标1将优化可生物降解的微粒的合成，以封装免疫调节因子。我们将测量和调整释放速率，以维持与生物学相关的浓度进行中介免疫调节。通过测量Treg的体外免疫型稳定性和细胞因子的产生，我们将评估释放因素的生物活性。 AIM 2将在小鼠牙周炎模型中测试微粒递送。我们将测量体内降解，并量化由Treg的局部增强。微粒。我们将通过测量相关的浓度进行功能测量使用基于组织形态的分析的细胞因子和组织注射。总体而言，实验将评估体内Treg扩张和稳定对PD注射的可行性。 PI是一个具有药物输送，组织工程和免疫学专业知识的新研究者，并将与 Co-I是一种具有自身免疫性疾病专业知识的临床科学家，重点是感染诱导的 Treg不稳定性导致炎症细胞因子的致病产生。该项目的结果将评估微粒介导的PD炎性T细胞调节的可行性，并导致R01 授予应用以全面的特征，以持久控制慢性的免疫调节 PD的炎症。