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（申请人提供）： 孕妇更容易出现牙龈炎症加剧，即妊娠期牙龈炎。怀孕期间的炎症和口腔病原菌的浸润，会危害孕妇的健康，影响其生活质量。在某些情况下，使用改良的结扎诱发牙周病模型，我们的初步数据表明，怀孕期间的牙龈炎症与Tregs（T细胞的一个子集）数量减少有关。该提议提出，宿主 Treg 会因病原体感染而增殖，以防止过度的免疫反应，但这一过程在怀孕期间会下调，从而导致免疫稳态被破坏。在目标 1 中，我们将使用体外分析和体内小鼠模型来测试这一概念，以确定怀孕对病原体诱导的 Treg 数量和功能的影响。诱导性Tregs的数量和免疫抑制功能；目标2有望研究Tregs在妊娠期间牙龈炎症中的作用以及Tregs的消耗。将Treg细胞过继移植到怀孕小鼠体内，将揭示Treg细胞对牙龈炎症的影响，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查明该疾病的关键细胞类型，还为该疾病的发病机制和未来治疗提供信息，从而显着改善女性健康。此外，当前提案的另一个目标是加强研究和治疗。为我校学生提供培训环境，让更多学生接触口腔生物学研究的概念和技术，培养下一代科学家。

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