DC exosome therapy to resolve inflammatory bone loss and oral infection

项目摘要 牙周炎（PD）是一种骨退行性炎症性疾病，导致其他疾病的风险增加。 死亡率和发病率较高的疾病。我们在这里提出了一种新的免疫治疗方法， PD策略，使用细胞纳米颗粒，来自树突细胞的外来体（EXO）。树突状细胞是 作为适应性免疫反应的“导演”，它们的免疫功能可以用于治疗慢性疾病。 免疫介导的疾病，如癌症和自身免疫性疾病。这是第一次学习我们的知识， 使用来自树突细胞的表型稳定的外泌体治疗小鼠中的实验PD。我们的战略 由牙周组织中负责破坏性炎症性骨丢失的“重编程”免疫细胞组成 使用自定义DC exo。我们的策略是将DC exo直接注射到牙龈中，以靶向抗炎途径 在特定的免疫细胞，以防止/解决牙槽骨丢失。这些研究的总体目标是获得 更好地理解DC衍生的exo在体内和体外的小鼠模型中的免疫生物学， 实验性PD，并将这些发现与从患有PD的人中分离的exo相关。我们的目标是测试 假设：目标1。递送至PD病变的外源性DCexo在原位持续存在并重新编程受体 DC和T细胞参与小鼠体内实验性PD;目的2. DC exo保留分子货物， 通过受体结合和内吞作用重编程受体DC和T细胞;目的3.内源性外源性 患有PD的人含有与外源性治疗和PD发病机制直接相关的分子货物。未来目标 有：1. DC外排疗法在人类PD中的发展，2.唾液外分子货物的评估 用于PD和其他口腔疾病的诊断潜力

Project Abstract Periodontitis (PD) is a bone degenerative inflammatory disease that contributes to increased risk of other diseases with more serious mortality and morbidity profiles. We propose here a novel immune therapeutic strategy for PD, using cellular nano-particles, exosomes (EXO) from dendritic cells. Dendritic cells are the “directors” of the adaptive immune response, as such, their immune functions can be exploited to treat chronic immune-mediated diseases such as cancer and autoimmune diseases. This is first study to our knowledge to employ phenotypically stable exosomes from dendritic cells to treat experimental PD in mice. Our strategy consists of “reprograming” immune cells in the periodontium responsible for destructive inflammatory bone loss using custom DC exo. Our tactic is to inject DC exo directly into the gingiva, to target anti-inflammatory pathways in specific immune cells, to prevent/resolve alveolar bone loss. The overall objective of these studies to acquire a better understanding of the immunobiology of DC-derived exo in vivo and in vitro in the murine model of experimental PD, and relate these findings to exo isolated from humans with PD. Our aims are to test the hypotheses that: Aim 1. Exogenous DCexo delivered to the PD lesion persist in situ and reprogram recipient DCs and T cells involved in experimental PD in mice in vivo; Aim 2. DC exo preserve molecular cargo and reprogram acceptor DCs and T cells through receptor binding and endocytosis; Aim 3. Endogenous exo from humans with PD contain molecular cargo of direct relevance to exo therapy and PD pathogenesis. Future goals include: 1. the development of DC exo therapy for PD in humans, 2. assessment of salivary exo molecular cargo for diagnostic potential in PD and other oral diseases