The Rolde of IL-37b from Plasma Cells in Periodontitis Pathogenesis

浆细胞IL-37b在牙周炎发病机制中的作用

• 批准号: 9259063
• 负责人: Yizu Jiao
• 金额: $ 6.61万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9259063
• 关键词: Address; Adoptive Transfer; Affect; Alveolar Bone Loss; Anti-Inflammatory Agents; Anti-inflammatory; Arthritis; Atherosclerosis; Attenuated; Autologous; B-Lymphocytes; Binding; Bone Resorption; Cell Lineage; Cell Nucleus; Cells; Coculture Techniques; Code; Computer Retrieval of Information on Scientific Projects Database; Development; Diabetes Mellitus; Disease; Enzyme-Linked Immunosorbent Assay; Epithelium; Exhibits; Exons; Fellowship; Genes; Genetic Polymorphism; Gingiva; Gingival Crevicular Fluid; Goals; Homologous Gene; Human; Immune response; Immune system; In Vitro; Infection; Inflammatory; Inflammatory Response; Interleukin-1 beta; Interleukin-18; Interleukin-6; Intestines; Lentivirus Infections; Lesion; Leukocytes; Ligature; Literature; Mentors; Modeling; Morphology; Multiple Myeloma; Mus; Natural Immunity; Oral; Osteoblasts; Osteoclasts; Pathogenesis; Patients; Periodontal Diseases; Periodontitis; Plasma; Plasma Cells; Play; Production; Protein Isoforms; Recombinants; Reporting; Rheumatoid Arthritis; Role; Scheme; Severities; Signal Transduction; Source; System; Systemic disease; TRANCE protein; Testing; Tissues; Tooth Diseases; Tooth structure; Transgenic Mice; Transgenic Organisms; Variant; alveolar bone; bone loss; cytokine; extracellular; genetic variant; genome wide association study; in vivo; inhibitor/antagonist; loss of function; microbiota; novel; novel therapeutic intervention; pathogen; receptor; response

Summary: Periodontitis is a common and serious dental disease in which billions of people suffer. It not only causes irreversible alveolar bone-loss but also is associated with systemic diseases such as atherosclerosis, diabetes and rheumatoid arthritis. Periodontitis has been characterized as an inflammatory disease associated with the interaction between the oral microbiota and host immune system. Both the innate and adaptive components of up ∼60% the immune system are involved in the pathogenesis of periodontitis. As one of the key components of the adaptive immune system, B-lineage cells (B lymphocytes and plasma cells) make of the total leukocytes present in periodontal lesions and participate in the induction of pathological bone loss in chronic periodontitis. IL-37, a newly identified anti-inflammatory cytokine, indicated to associate with the severity of periodontitis by our genome-wide association study (GWAS). Furthermore, our preliminary studies found that IL-37b is the dominant isoform of IL-37 and highly expressed by plasma cells in the gingival tissue from periodontitis patients. These findings suggested strong correlation between IL-37b and plasma cells in periodontitis. However, the relationship among anti-inflammatory IL-37b, plasma cells and periodontitis remains completely unknown. The goal of this proposal is to gain a better understanding of the role of IL-37b from plasma cells in periodontitis progression. We propose three Specific Aims to explore the underlying mechanisms of the relationship among IL-37b, plasma cells and periodontitis in this study. (Aim 1): Investigate the role of IL-37b from plasma cells to regulate autologous RANKL production in periodontitis development. (Aim2): Investigate the role of IL-37b from plasma cells to suppress the differentiation of pre- osteoclasts into osteoclasts during periodontitis progression. (Aim3): Investigate the role of genetic variants of IL-37b from plasma cells during the progression of periodontitis. Considering the board anti-inflammatory activity, fully elucidating the mechanisms by which IL-37b regulates the pathogenesis of periodontists may highlight a new therapeutic approach for periodontal disease.

概括： 牙周炎是一种常见且严重的牙科疾病，其中数十亿人受苦。它不仅导致 不可逆的肺泡骨损伤，但也与全身性疾病（例如动脉粥样硬化，糖尿病）有关 和类风湿关节炎。牙周炎的特征是与 口服微生物群和宿主免疫系统之间的相互作用。既有的先天和适应性组成部分 高达60％ 免疫系统参与牙周炎的发病机理。作为 自适应免疫系统，B型细胞（B淋巴细胞和浆细胞）构成总计 牙周病变中存在的白细胞并参与慢性病理骨质损失的诱导 牙周炎。 IL-37是一种新鉴定的抗炎细胞因子，该因子与严重程度有关 我们的全基因组协会研究（GWAS）的牙周炎。此外，我们的初步研究发现 IL-37b是IL-37的主要同工型，并由牙龈组织中的血浆细胞高度表达 牙周炎患者。这些发现表明IL-37B与浆细胞之间的相关性很强 牙周炎。但是，抗炎IL-37B，浆细胞和牙周炎之间的关系 仍然完全未知。该提案的目的是更好地了解IL-37B的作用 来自牙周炎进展的浆细胞。我们提出了三个特定的目标，以探索基础 在这项研究中，IL-37B，浆细胞和牙周炎之间关系的机制。 （AIM 1）： 研究浆细胞中IL-37b在调节牙周炎中自体RANKL产生的作用 发展。 （AIM2）：研究IL-37B从等离子体细胞抑制前的分化的作用 牙周炎进展过程中破骨细胞成破骨细胞。 （AIM3）：研究遗传变异的作用 牙周炎进展过程中浆细胞的IL-37b。考虑董事会抗炎 活动，完全阐明IL-37B调节牙周病患者的机制 突出显示一种新的牙周疾病治疗方法。