Origin and function of atypical lymphocyte populations in inflamed tissue in SLE and RA

SLE 和 RA 炎症组织中非典型淋巴细胞群的起源和功能

• 批准号: 10427145
• 负责人: Betty Diamond
• 金额: $ 49.84万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-15 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10427145
• 关键词: Address; Age; Antibodies; Antigen-Presenting Cells; Antigenic Specificity; Antigens; Atypical lymphocyte; Autoantibodies; Autoimmune Diseases; Autoimmunity; B-Cell Antigen Receptor; B-Cell Development; B-Lymphocytes; BLR1 gene; Blood; CD4 Positive T Lymphocytes; CD8-Positive T-Lymphocytes; Cell Survival; Cell physiology; Cells; Complement 3d Receptors; Derivation procedure; Development; Disease; Exhibits; Family; Fibroblasts; Frequencies; Helper-Inducer T-Lymphocyte; Heterogeneity; Homing; Human; ITGAX gene; Immune; Immunologics; Immunology; In Situ; Kidney; Knowledge; Lupus; Lymphocyte; Lymphoid; Maps; Mediator of activation protein; Memory B-Lymphocyte; Myeloid Cells; Natural Killer Cells; Pathogenicity; Pathway interactions; Patients; Peripheral; Phenotype; Plasma Cells; Plasmablast; Population; Process; Production; Resolution; Rheumatoid Arthritis; Stromal Cells; Syndrome; Synovial Fluid; Synovial Membrane; System; Systemic Lupus Erythematosus; T-Lymphocyte; T-Lymphocyte Subsets; Tissues; Work; chemokine; chemokine receptor; chronic autoimmune disease; cytokine; design; new therapeutic target; synergism; targeted treatment; transcriptome; transcriptomics

A high-resolution analysis of cells in inflamed tissue offers the possibility of uncovering previously unappreciated pathogenic mechanisms and of identifying new therapeutic targets. In this project, we will characterize age/autoimmunity associated B cells (ABCs) in kidney and synovium of patients with systemic lupus and rheumatoid arthritis, respectively. We will explore their heterogeneity, derivation, localization, and antigenic targets as well as their functional interactions with T cell subsets, most specifically T follicular and T peripheral helper cells (Tfh/Tph). These efforts will provide a broad assessment of the features and potential functions of this highly expanded B cell population in human autoimmunity.

对发炎组织中细胞的高分辨率分析提供了发现先前的可能性 未被认识的致病机制和确定新的治疗靶点。 在这个项目中，我们将表征肾脏和滑膜中的年龄/自身免疫相关 B 细胞 (ABC) 分别患有系统性狼疮和类风湿性关节炎的患者。我们将探索它们的异质性， 衍生、定位和抗原靶标以及它们与 T 细胞亚群的功能相互作用，大多数 特别是滤泡 T 细胞和外周辅助 T 细胞 (Tfh/Tph)。这些努力将提供广泛的评估 这种高度扩增的 B 细胞群在人类自身免疫中的特征和潜在功能。