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齿疾病，数十亿人深受其苦。 不可逆的牙槽骨丢失，但也与动脉粥样硬化、糖尿病等全身性疾病有关 和类风湿性关节炎已被定性为与牙周病相关的炎症性疾病。 口腔微生物群与宿主免疫系统之间的相互作用。 上涨~60% 免疫系统是牙周炎发病的关键组成部分之一。 适应性免疫系统、B 谱系细胞（B 淋巴细胞和浆细胞）组成 白细胞存在于牙周病变中并参与诱导慢性牙病性骨丢失 IL-37是一种新发现的抗炎细胞因子，表明与牙周炎的严重程度有关。 此外，我们的全基因组关联研究（GWAS）发现牙周炎。 IL-37b 是 IL-37 的主要亚型，在牙龈组织中的浆细胞中高度表达 这些发现表明，IL-37b 与牙周炎患者的浆细胞之间存在很强的相关性。 然而，抗炎IL-37b、浆细胞与牙周炎之间的关系。 该提案的目的是更好地了解 IL-37b 的作用。 我们提出了三个具体目标来探索牙周炎进展中的浆细胞。 本研究中IL-37b、浆细胞和牙周炎之间关系的机制（目标1）： 研究浆细胞 IL-37b 在调节牙周炎中自体 RANKL 产生中的作用 (目标 2)：研究浆细胞中的 IL-37b 抑制前细胞分化的作用。 破骨细胞在牙周炎进展过程中转变为破骨细胞（目标3）：研究基因变异的作用。 考虑到牙周炎进展期间浆细胞中的 IL-37b 具有抗炎作用。 活性，充分阐明IL-37b调节牙周病发病机制的机制可能 强调牙周病的新治疗方法。