Regulatory B cells in periodontal disease

项目摘要。 我们的亲本R01资助(DE025255)的目的是确定B10介导的抑制 牙周病的炎症与牙周骨吸收。到目前为止，我们的数据已经证明 促进局部B10功能是可以实现的，并且B10的局部渗透需要抗原特异性 细胞。我们目前正在研究传递B10最终功能的免疫调节成分 免疫细胞-细胞相互作用背景下的激活，以及这种相互作用的变化可能如何影响疾病 结果。这些信息很重要，因为它允许我们设计最佳策略来协同免疫 调节功能，恢复健康，最大限度地减少免疫激活/抑制的不良副作用。 然而，我们认识到，由于缺乏所需的专门知识和资源，实现这些目标面临挑战。 在我们手中。为了克服这样的挑战，我们将利用新建立的合作 私家侦探和哈佛大学牙医学院助理教授科尼利乌·西马博士之间的合作。司马医生是 具有单核/巨噬细胞生物学专业知识的早期研究人员(ESI)，并已开发出优化 活体牙龈显微镜检测牙周组织中白细胞的募集和表型 疾病。与体内成像系统(IVIS)一起，我们将能够检测和跟踪局部相互作用 牙龈组织中B10和巨噬细胞之间的相互作用。我们的假设是B10激活促进巨噬细胞 调节/抗炎和促分解表型的激活，这有助于减少 发炎和骨质流失。为了验证这一假设，我们将首先确定激活的B10细胞对 应用细胞共培养系统体外培养巨噬细胞表型(目标1)。然后我们将研究巨噬细胞 应用IVIS和活体显微镜观察B10过继移植后的表型转换和牙周炎 (目标2)。总而言之，与本论坛目标一致的要点如下： 1.该方案是与ESI的合作，旨在探索协同作用的新机制 在先天免疫(司马博士)和获得性免疫(韩博士)之间。 2.扩展我们的假设，利用亲本R01的PI所不具备的技术，这是一个重要的 在原目标范围内加强。 3.利用高灵敏度、高分辨率的尖端细胞成像技术进行填充 用于免疫学研究的口腔病变的精确成像的差距。 4.如果成功，将有利于双方合作研究人员未来的R01应用。 5.提案中的合作者没有任何过去的合作记录。 6.不拟从该基金为投资主任分配薪金。

Project Summary. The objective of our parent R01 grant (DE025255) is to determine the mechanism of B10-mediated inhibition of inflammation and periodontal bone resorption in periodontal disease. So far, our data have demonstrated that promoting local B10 function is achievable and that antigen specificity is required for the local infiltration of B10 cells. We are currently investigating the immune regulatory components that relay the ultimate function of B10 activation, in the context of immune cell-cell interaction, and how changes in such interactions may affect disease outcome. Such information is important because it allow us to design optimal strategies to synergize immune regulatory function to restore health and minimize untoward side effects of immune activation/inhibition. However, we realized the challenge to achieve these goals due to the lack of required expertise and resources at our hands. To overcome such challenge, we will take advantage of the newly established collaboration between the PI and Dr. Corneliu Sima, Assistant Professor at Harvard School of Dental Medicine. Dr. Sima is an early stage Investigator (ESI) with expertise in monocyte/macrophage biology and has developed optimized intravital gingival microscopy assays for assessment of leukocyte recruitment and phenotype in periodontal disease. Together with the in vivo imaging system (IVIS), we will be able to detect and trace local interactions between B10 and macrophages in gingival tissues. Our hypothesis is that B10 activation promotes macrophage activation toward a regulatory/anti-inflammatory and pro-resolving phenotype, which contribute to the reduced inflammation and bone loss. To test this hypothesis, we will first determine the effect of activated B10 cells on Macrophage phenotype in vitro using a cell co-culture system (Aim 1). Then we will investigate the Macrophage phenotype switching and gingival inflammation after adoptive B10 transfer using IVIS and intravital microscopy (Aim 2). In summary, the points aligned with the goal of this FOA are the following: 1. This proposal is a collaboration with an ESI to explore novel mechanism of synergistic interaction between innate (Dr. Sima) and adaptive immunity (Dr. Han). 2. Extend our hypothesis and utilize techniques unavailable to PI of the parent R01, which is an important enhancement within the scope of the original Aims. 3. Take advantage of the cutting-edge cell imaging technologies with high sensitivity and resolution to fill the gap of precision imaging of oral lesions used in immunology research. 4. If successful, it will benefit both collaborative investigators for future R01 applications. 5. The collaborators in the proposal don't have any past record of collaboration. 6. No proposed salary allocation for PIs from this fund.