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Cytokine Dysregulation in Autoimmune Hemolytic Anemia

自身免疫性溶血性贫血中的细胞因子失调

基本信息

批准号：
8532955
负责人：
Katrina K Hoyer
金额：
$ 23.26万
依托单位：
UNIVERSITY OF CALIFORNIA, MERCED
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-01 至 2015-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8532955
关键词：
Acute Address Age Animals Antibodies Antibody Formation Antibody Specificity Antigen Targeting Antigens Applications Grants Area Atypical lymphocyte Autoantibodies Autoantigens Autoimmune Diseases Autoimmune Process Autoimmune hemolytic anemia Autoimmunity Award B Cell Proliferation B-Lymphocytes CD4 Positive T Lymphocytes Cell Communication Cell Extracts Cell Separation Cells Cessation of life Clinical Markers Collecting Cell Cytokine Signaling Data Dendritic Cells Dendritic cell activation Development Diagnostic Disease Disease Progression Employee Strikes Environment Erythrocytes Evolution Future Gene Family Genes Genetic Models Goals Grant Human Hybridomas Immune Immune System Diseases Immunization Immunoglobulin Class Switching Immunologic Memory Immunology Infection Inflammation Interferons Interleukin-12 Interleukin-2 Journals Knockout Mice Lymphocyte Lymphocyte Count Lymphoid Tissue Lymphoproliferative Disorders Manuscripts Mediating Methods Modeling Molecular Weight Mono-S Multiple Pregnancy Mus Peripheral Phase Phenotype Play Process Production Proteins Published Comment RNA Reaction Reagent Regulation Regulatory T-Lymphocyte Research Proposals Role Sampling Secondary to Self Tolerance Serum Severity of illness Signal Pathway Specificity Stimulus Suggestion Surface T-Cell Activation T-Cell Receptor T-Lymphocyte Testing Time Tissues Transgenic Mice Western Blotting anergy autoreactive T cell base cytokine insight killings lymph nodes migration mouse model overexpression prevent research study response screening tool

项目摘要

Autoimmune hemolytic anemia (AIHA) is characterized by the production of antibodies directed against self red blood cells. Given the frequent association between AIHA and other autoimmune disorders, generalized immune dysfunction likely plays a role in the disease process. Under normal conditions, self-reactive lymphocytes are killed, inactivated or suppressed by regulatory T cells, resulting in unresponsiveness to selfantigens. Disruption of these control mechanisms results in the survival and pathogenic activation of selfreactive lymphocytes. It is unclear how self-reactive lymphocytes are spontaneously activated in the absence of overt infection or other stimuli, leading to autoimmune disease. If the initiators of activation and subsequent disease can be delineated, and the antigen targets of pathogenic antibodies identified, means of controlling these autoimmune reactions may be uncovered. In this study, we use a mouse model of spontaneous, acute systemic autoimmunity that principally manifests as AIHA to define the stimuli that are required for the development of autoimmune disease. The overall objective of this proposal is to define the immunological abnormalities in a model of spontaneous autoimmunity and to identify the target antigens in this disease. The central hypothesis underlying this proposal is that abnormal cytokine production and uncontrolled activation of dendritic cells due to the absence of regulatory T cell suppression results in autoimmunity. The successful completion of this project will elucidate the immune abnormalities (including the role of dendritic cells, cytokines and antigen-specific lymphocytes) in AIHA development, and strengthen our understanding of what triggers and maintains autoimmunity.

自身免疫性溶血性贫血（AIHA）的特点是产生针对自身的抗体