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Function of Blimp1/prdm-1 in dendritic cells in the generation of autoantibodies

树突状细胞中Blimp1/prdm-1在自身抗体生成中的功能

基本信息

批准号：
8683106
负责人：
Sun Jung Kim
金额：
$ 5.72万
依托单位：
FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-02 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8683106
关键词：
Ablation Adoptive Transfer Affect Age-Months Antibodies Autoantibodies Autoimmune Diseases Autoimmunity B-Lymphocytes Belief Blood Bone Marrow CD4 Positive T Lymphocytes Cell physiology Cells Cellular biology Cessation of life Clinic Clinical Data Dendritic Cells Development Disease Effector Cell Estradiol Estrogens Exhibits Female Frequencies Generations Helper-Inducer T-Lymphocyte ITGAX gene Immune Immune Tolerance Immune system Immunoglobulin G Immunoglobulin M Implant In Vitro Inflammation Inflammatory Injury Lead Lupus Measures Mediating Modeling Mus Mutation Nuclear Organ Pattern Phagocytosis Phenotype Placebos Production Regulation Role Serologic tests Serum Somatic Mutation Spleen Splenomegaly Structure of germinal center of lymph node Systemic Lupus Erythematosus T-Lymphocyte Testing Tissues Toll-like receptors Weight Wild Type Mouse Woman autoreactive B cell autoreactivity cytokine human disease immune activation in vivo lupus-like male men new therapeutic target novel precursor cell prevent response

项目摘要

DESCRIPTION (provided by applicant): Systemic Lupus (SLE) is an autoimmune disease characterized by the production of an array of anti- nuclear antibodies that affects women far more frequently than men. Abnormal B and T cell function has been extensively studied in murine models of SLE. We have developed a mouse with a deletion of Blimp-1 function uniquely in dendritic cells. Female mice develop a lupus-like serology while male mice do not. We propose to understand the alterations in dendritic cell function and the mechanism for the subsequent dysregulation of B cell function. Furthermore, we will determine why this genetic defect manifests as autoimmunity only in female mice. These studies will further our understanding of dendritic cell biology and may identify a new therapeutic target in SLE.

描述(申请人提供)：系统性红斑狼疮(SLE)是一种自身免疫性疾病，其特征是产生一系列抗核抗体，女性比男性更容易受到影响。在系统性红斑狼疮小鼠模型中，B和T细胞功能异常已被广泛研究。我们已经开发出一种树突状细胞特有的Blimp-1功能缺失的小鼠。雌性小鼠会产生狼疮样的血清学，而雄性小鼠不会。我们建议了解树突状细胞功能的改变以及随后B细胞功能失调的机制。此外，我们将确定为什么这种遗传缺陷只在雌性小鼠身上表现为自身免疫。这些研究将加深我们对树突状细胞生物学的理解，并可能确定SLE的新治疗靶点。