Plasma Cell Regulation by Purinergic Receptors

嘌呤能受体对浆细胞的调节

基本信息

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
项目类别：
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&apos ,4&apos -disulfonic acid receptor

项目摘要

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.

项目概要分泌针对自身抗原的抗体的浆细胞对人体构成相当大的威胁人类健康。此外，由于许多浆细胞的寿命特别长，需要采取策略来消耗分泌致病性的长寿命浆细胞（LLPC）抗体。该项目的中心假设是骨髓中的 LLPC 产生通过检测细胞外 ATP 的特定成员来获取必需的生存信号嘌呤能受体 (P2rX) 家族。因此，我们建议选择性化合物毒物相关的嘌呤能受体会耗尽 LLPC。为了检验我们的假设，我们将： 1) 确定 P2rX 抑制剂对 LLPC 生成和维持的影响，以及 2) 确定嘌呤能受体 P2rX4 在早期浆细胞诱导和有限责任公司维护。这些研究将提供独特且必要的见解有限责任公司采用的专门生存机制。这项工作支持我们的长期制定战略的目标是有效和具体地禁用或耗尽有问题的浆细胞。