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

Treg 调节及其在妊娠期牙龈炎症中的作用（行政补充）

• 批准号: 9237746
• 负责人: Shuang Liang
• 金额: $ 10万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-15 至 2020-01-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9237746
• 关键词: Administrative Supplement; Adoptive Transfer; Affect; Animal Model; Bacteria; Cells; Communicable Diseases; Data; Development; Disease; Disease model; Down-Regulation; Environment; Flow Cytometry; Fostering; Funding; Future; Gingiva; Gingivitis; Goals; Health; Hemorrhage; Homeostasis; Immune; Immune response; Immunity; In Vitro; Infection; Infiltration; Inflammation; Knockout Mice; Ligation; Link; Lymphocyte Subset; Mus; Natural Immunity; Oral; Pathogenesis; Pathway interactions; Patients; Periodontal Diseases; Pregnancy; Pregnant Women; Prevalence; Process; Proliferating; Quality of life; Regulation; Regulatory T-Lymphocyte; Research; Research Training; Role; School Dentistry; Schools; Scientist; Students; T-Cell Proliferation; T-Lymphocyte; T-Lymphocyte Subsets; Technology; Testing; Thymus Gland; Tissues; Universities; Women' s Health; Work; adaptive immunity; adverse pregnancy outcome; cell type; improved; in vivo; insight; mouse model; next generation; novel; oral bacteria; oral biology; oral immunology; pathogen; pathogenic bacteria; pregnant; prevent; programs; response; therapeutic target; transcription factor

 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.

 描述（由适用提供）：孕妇更容易发生加重的牙龈感染，这被称为妊娠牙龈炎。怀孕期间的炎症和口腔致病性细菌浸润对孕妇的健康有害，并对其生活质量产生负面影响，在某些情况下可能会引起不良怀孕的结果。使用修饰的连接诱导的牙周疾病模型，我们的初步数据意味着怀孕期间的牙龈炎症与较低的Tregs有关，TREG数量较低，T细胞的一个子集对于宿主免疫调节至关重要。该提议假设宿主因病原体感染而增殖以防止过量的免疫调查，但该过程在怀孕期间被下调。 Treg开发的这种下调是导致免疫稳态和牙龈炎症的破坏。该概念将使用体外分析和体内小鼠模型进行测试。在AIM 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。怀孕小鼠将结扎并感染病原体，以确定诱导Treg的数量以及免疫抑制功能；还将确定对Treg增殖的调节的详细机制。 AIM 2有望研究Treg在怀孕期间牙龈炎症中的作用。 Tregs的耗竭以及将Treg的自适应转移到怀孕小鼠中，将揭示Tregs对牙龈感染的影响。目的是揭示通过怀孕状况对感染引起的Treg发育的调节，以及该调节对怀孕期间牙龈感染的影响。该项目的目的不仅是指出疾病中的关键细胞类型，还为疾病的发病机理和未来治愈提供信息，从而显着改善女性健康。此外，当前建议的另一个目标是通过使更多的学生了解口头生物学研究的概念和技术，并培养下一代科学家，从而增强我们学校的学生的研究和培训环境。

项目成果

Roles of Porphyromonas gingivalis and its virulence factors in periodontitis.

• DOI: 10.1016/bs.apcsb.2019.12.001
• 发表时间: 2020
• 期刊: Advances in protein chemistry and structural biology
• 作者: Xu W;Zhou W;Wang H;Liang S
• 通讯作者: Liang S