Microparticles Modulating Regulatory T cells in Periodontal Disease

项目总结 牙周病是一种以牙龈感染、结缔组织感染为特征的慢性炎症性疾病 组织和牙槽骨。帕金森病以密集的免疫细胞浸润为特征，其中T细胞是关键 是宿主反应的中介物，也是帕金森病进展的重要参与者。在参与的T中 细胞亚群，调节性T细胞(Treg)已在帕金森病患者的组织中被发现，通常功能是 抑制促炎T细胞。然而，在慢性炎症性病变中，Treg可能会失去免疫调节 功能，相反，产生促炎细胞因子。我们假设恢复Treg功能将 影响帕金森病患者的免疫反应。为了验证这一假设，该项目将开发免疫调节剂 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 优化可生物降解微球的合成，用于包裹免疫调节因子。我们会 测量和调整释放率以维持与生物相关的介体浓度 免疫调节。通过测量Treg的体外免疫表型稳定性和细胞因子的产生，我们将 评估释放的因子的生物活性。目标2将在小鼠牙周炎模型中测试微粒传递。 我们将测量体内降解，并量化局部增强的Treg由 微粒。我们将通过测量相关的浓度来进行功能测量 基于组织形态计量学的细胞因子和组织炎症分析。总体而言，这些实验将 评价体内Treg扩增和稳定化治疗帕金森病炎症的可行性。PI是一种 在药物输送、组织工程和免疫学方面具有专业知识的新调查员，将与 Co-I，一位在自身免疫性疾病方面拥有专业知识的临床科学家，重点研究炎症是如何诱导的 Treg不稳定导致致病性炎性细胞因子的产生。该项目的结果将 评估微粒介导的炎性T细胞在帕金森病中的可行性，并导致R01 授权应用全面表征免疫调节对慢性阻塞性肺疾病的持久控制 帕金森病的炎症反应。

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.