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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：
10240081
负责人：
David M Allman
金额：
$ 24.38万
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 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10240081
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/antagonist 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.

项目总结分泌自身抗原抗体的浆细胞对人类构成相当大的威胁人类健康。此外，由于许多浆细胞的寿命非常长，需要策略来耗尽分泌致病物质的长寿命浆细胞(LLPC) 抗体。这个项目的中心假设是，骨髓中的LLPC产生通过感知细胞外的ATP与特定的成员嘌呤能受体(P2rX)家族。因此，我们建议选择性地毒物相关的嘌呤能受体将耗尽LLPC。为了检验我们的假设，我们将： 1)确定P2rX抑制剂对LLPC产生和维持的影响，以及2) 确定嘌呤能受体P2rX4在早期浆细胞诱导和分化中的作用 LLPC维护。这些研究将提供独特和必要的洞察 LLPC使用的专门生存机制。这项工作支持了我们长期的制定有效和具体禁用或耗尽的战略的目标有问题的浆细胞。