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

基本信息

批准号：
10598097
负责人：
Betty Diamond
金额：
$ 62.67万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
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：
2021-06-15 至 2026-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10598097
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 Communication 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 Infiltration Inflammatory Kidney Knowledge Lupus Lymphocyte Lymphoid Maps Mediator 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 candidate identification chemokine chemokine receptor chronic autoimmune disease cytokine design interleukin-21 new therapeutic target synergism targeted treatment transcriptome transcriptomics

项目摘要

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。