Treg regulation and its role in gingival inflammation during pregnancy (Administrative Supplements)

 描述（由申请人提供）：孕妇更容易发生牙龈炎症加重，称为妊娠牙龈炎。妊娠期间的炎症和口腔病原菌浸润对孕妇的健康有害，对她们的生活质量产生负面影响，在某些情况下会导致不良的妊娠结局。使用改良的结扎诱导的牙周病模型，我们的初步数据表明，怀孕期间的牙龈炎症与TcB数量减少有关，TcB是对宿主免疫调节至关重要的T细胞亚群。这一提议假设宿主T细胞增殖以响应病原体感染，以防止过度的免疫反应，但该过程在妊娠期间下调。Treg发育的这种下调是导致免疫稳态破坏和牙龈炎症的原因。将使用体外分析和体内小鼠模型来测试这一概念。在目的1中，我们将确定妊娠对病原体诱导的Treg数量和功能的影响。将妊娠小鼠结扎并感染病原体，以确定诱导的Treg的数量以及免疫抑制功能;还将确定调节Treg增殖的详细机制。目的2探讨妊娠期牙龈炎中TGFAP的表达及意义。TdR的消耗以及TdR过继转移到妊娠小鼠中将揭示TdR对牙龈炎症的作用。目的是揭示妊娠状态对感染诱导的Treg发育的调节，以及这种调节对妊娠期间牙龈炎症的影响。该项目的目标不仅是确定疾病的关键细胞类型，而且还为疾病的发病机制和未来治疗提供信息，从而大大改善妇女健康。此外，本建议的另一个目的是通过让更多学生接触口腔生物学研究的概念和技术，加强我校学生的研究和培训环境，培养下一代科学家。

 DESCRIPTION (provided by applicant): Pregnant women are more prone to develop exacerbated gingival inflammation, which is known as pregnancy gingivitis. Inflammation and oral pathogenic bacteria infiltration during pregnancy are detrimental to pregnant women's health and negatively impact on their life quality, and can cause adverse pregnancy outcomes in some cases. Using a modified ligation induced periodontal disease model, our preliminary data implies that the gingival inflammation during pregnancy is linked with lower number of Tregs, one subset of T cells critical for host immune regulation. This proposal hypothesizes that host Tregs proliferate in response to pathogen infection to prevent excessive immune responses, but the process is down-regulated during pregnancy. This down-regulation of Treg development is responsible for the disrupted immune homeostasis and gingival inflammation. This notion will be tested using in vitro analysis and in vivo mouse model. In Aim 1, we will determine the effect of pregnancy on pathogen-induced Treg number and function. Pregnant mice will be ligated and infected with pathogens to determine the number as well as the immune suppressive function of induced Tregs; detailed mechanisms of the regulation on Treg proliferation will also be determined. Aim 2 is expected to investigate the role of Tregs in the gingival inflammation during pregnancy. Depletion of Tregs, as well as adoptive transfer of Tregs into pregnant mice, will reveal the effect of Tregs on the gingival inflammation. The objective is to reveal the regulation of infection-induced Treg development by pregnancy status, and the effect of this regulation on gingival inflammation during pregnancy. The goal of the project is to not only pinpoint the critical cell type in the disease, but also provide information for the pathogenesis and future cure of the disease, therefore significantly improving woman health. Moreover, another goal of current proposal is to enhance the research and training environment for the students in our school by exposing more students to the concept and technologies for oral biology research and foster next generation of scientists.