Plasma Cell Regulation by Purinergic Receptors

嘌呤能受体对浆细胞的调节

• 批准号: 10441466
• 负责人: David M Allman
• 金额: $ 20.31万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10441466
• 关键词: ATP Receptors; Antibodies; Antibody titer measurement; Autoantigens; Autoimmune Diseases; Autoimmunity; B-Lymphocytes; Binding; Bone Growth; Bone Marrow; CD8-Positive T-Lymphocytes; Cartilage; Cations; Cell Count; Cell Maintenance; Cell Survival; Cell physiology; Cells; Chondrocytes; Chronic; Clinical; Connexins; Data; Defect; Elements; Exhibits; Extracellular Space; Family; G-Protein-Coupled Receptors; Generations; Graft Rejection; Health; Human; Immunoglobulin-Secreting Cells; Induced Mutation; Knockout Mice; Longevity; Maintenance; Membrane; Memory; Messenger RNA; Molecular; Mutant Strains Mice; Odontoblasts; Osteoblasts; Pathogenicity; Pharmaceutical Preparations; Plasma Cells; Poison; Purinoceptor; Regulation; Role; Serum; Signal Pathway; Signal Transduction; Spleen; Testing; Tissues; Tooth structure; Transplantation; Vaccine Design; Vertebrates; Work; base; bone; chronic pain; extracellular; immune activation; improved; improved outcome; inhibitor; insight; member; mineralization; mutant; novel; novel strategies; novel therapeutic intervention; novel therapeutics; osteoblast differentiation; plasma cell differentiation; pyridoxal phosphate-6-azophenyl-2' ,4' -disulfonic acid; receptor

Project summary Plasma cells that secrete antibodies against self-antigens pose a considerable threat to human health. Moreover, because many plasma cells are exceptionally long-lived, strategies are needed to deplete long-lived plasma cells (LLPCs) that secrete pathogenic antibodies. This project centers on the hypothesis that LLPCs in bone marrow generate requisite survival signals by sensing extracellular ATP with specific members of the purinergic receptor (P2rX) family. Hence, we propose that compounds that selectively poison relevant purinergic receptors will deplete LLPCs. To test our hypothesis, we will: 1) Establish the impact of P2rX inhibitors on LLPC generation and maintenance, and 2) Determine the role of the purinergic receptor P2rX4 in early plasma cell induction and LLPC maintenance. These studies will provide unique and needed insights into the specialized survival mechanisms employed by LLPCs. This work supports our long-term objective of developing strategies to effectively and specifically disable or deplete problematic plasma cells.

项目总结