Regulatory B cells in periodontal disease

牙周病中的调节性 B 细胞

• 批准号: 9903616
• 负责人: Xiaozhe Han
• 金额: $ 30.85万
• 依托单位: ADA FORSYTH INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-06-13 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9903616
• 关键词: Acute; Adoptive Transfer; Affect; Anatomy; Anti-inflammatory; Antigens; B-Lymphocytes; Biological Assay; Biology; Bone Marrow; Bone Resorption; Cell Communication; Cells; Coculture Techniques; Collaborations; Competence; Data; Dental Schools; Disease; Disease Outcome; Enzyme-Linked Immunosorbent Assay; Experimental Models; Flow Cytometry; Funding; Future; Gingiva; Goals; Grant; Hand; Health; Image; Imaging technology; Immune; Immune response; Immunohistochemistry; Immunology; In Vitro; Infiltration; Inflammation; Inflammatory Response; Investigation; Label; Leukocytes; Ligature; Macrophage Activation; Manuscripts; Mediating; Medicine; Microscopy; Monitor; Mus; Parents; Pattern; Periodontal Diseases; Periodontitis; Phagocytosis; Phenotype; Physiology; Research; Research Personnel; Resolution; Resources; Specificity; System; TNF gene; Techniques; Testing; Tissues; Wages; Work; adaptive immunity; base; bone loss; cellular imaging; cytokine; design; imaging modality; immune activation; immunoregulation; in vivo; in vivo imaging; in vivo imaging system; innovation; insight; intravital microscopy; macrophage; monocyte; mouse model; novel; oral lesion; professor; programs; recruit; side effect; trafficking

Project Summary. The objective of our parent R01 grant (DE025255) is to determine the mechanism of B10-mediated inhibition of inflammation and periodontal bone resorption in periodontal disease. So far, our data have demonstrated that promoting local B10 function is achievable and that antigen specificity is required for the local infiltration of B10 cells. We are currently investigating the immune regulatory components that relay the ultimate function of B10 activation, in the context of immune cell-cell interaction, and how changes in such interactions may affect disease outcome. Such information is important because it allow us to design optimal strategies to synergize immune regulatory function to restore health and minimize untoward side effects of immune activation/inhibition. However, we realized the challenge to achieve these goals due to the lack of required expertise and resources at our hands. To overcome such challenge, we will take advantage of the newly established collaboration between the PI and Dr. Corneliu Sima, Assistant Professor at Harvard School of Dental Medicine. Dr. Sima is an early stage Investigator (ESI) with expertise in monocyte/macrophage biology and has developed optimized intravital gingival microscopy assays for assessment of leukocyte recruitment and phenotype in periodontal disease. Together with the in vivo imaging system (IVIS), we will be able to detect and trace local interactions between B10 and macrophages in gingival tissues. Our hypothesis is that B10 activation promotes macrophage activation toward a regulatory/anti-inflammatory and pro-resolving phenotype, which contribute to the reduced inflammation and bone loss. To test this hypothesis, we will first determine the effect of activated B10 cells on Macrophage phenotype in vitro using a cell co-culture system (Aim 1). Then we will investigate the Macrophage phenotype switching and gingival inflammation after adoptive B10 transfer using IVIS and intravital microscopy (Aim 2). In summary, the points aligned with the goal of this FOA are the following: 1. This proposal is a collaboration with an ESI to explore novel mechanism of synergistic interaction between innate (Dr. Sima) and adaptive immunity (Dr. Han). 2. Extend our hypothesis and utilize techniques unavailable to PI of the parent R01, which is an important enhancement within the scope of the original Aims. 3. Take advantage of the cutting-edge cell imaging technologies with high sensitivity and resolution to fill the gap of precision imaging of oral lesions used in immunology research. 4. If successful, it will benefit both collaborative investigators for future R01 applications. 5. The collaborators in the proposal don't have any past record of collaboration. 6. No proposed salary allocation for PIs from this fund.

项目总结。