HIPK1：SLE 的新免疫调节靶点-猫眼课题宝

HIPK1：SLE 的新免疫调节靶点

批准号：

10647292

负责人：

ANDREW D WELLS

金额：

$26.7万

依托单位：

CHILDREN'S HOSP OF PHILADELPHIA

依托单位国家：

美国

项目类别：

财政年份：

2023

资助国家：

美国

项目状态：

未结题

起止时间：

2023-07-25 至 2025-06-30

来源：

https://reporter.nih.gov/project-details/10647292

关键词：

3-Dimensional Affect Affinity American Antibodies Antibody Formation Antibody Response Antigens Autoantibodies Autoimmune Diseases Autoimmunity B cell differentiation B-Lymphocytes BCL6 gene BLR1 gene Biology Blood Cell Lineage Cell Nucleus Cells Chickens Chromosome Mapping Clustered Regularly Interspaced Short Palindromic Repeats Code Collaborations Communicable Diseases Development Disease Drug Modulation Drug Targeting Enzymes Foundations Functional disorder Future Generations Genes Genetic Genetic Polymorphism Genetic Variation Genetic study Genome Genomics Health Helper-Inducer T-Lymphocyte Homeostasis Human Humoral Immunities IL7R gene Immune Immune response Immunity Immunization Immunoglobulin Class Switching Immunomodulators Immunophenotyping In Vitro Infection Inflammation Inherited Knockout Mice LoxP-flanked allele Lupus Lymphocyte Lymphoid Malignant Neoplasms Maps Mediating Modeling Molecular Morbidity - disease rate Mus Mutation Organoids Outcome Outcome Study Ovalbumin Patients Pharmacology Study Phosphotransferases Predisposition Production Publishing Regulation Regulatory Element Role Series Structure of germinal center of lymph node System Systemic Lupus Erythematosus T cell differentiation T cell regulation T-Cell Development T-Lymphocyte TLR7 gene Testing Tonsil Untranslated RNA Vaccination Vaccines Variant Work adaptive immunity antigen-specific T cells autoinflammatory diseases cell type cytokine efficacy study gain of function genome wide association study high risk human model immunoregulation in vivo insight interleukin-21 loss of function mortality mouse model mutant novel novel therapeutic intervention pediatric patients pharmacologic programmed cell death protein 1 response single-cell RNA sequencing systemic autoimmune disease systemic inflammatory response three dimensional structure transcriptomics variant of unknown significance women of color young woman

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ABSTRACT Our prior work using physical maps of systemic lupus erythematosus (SLE)-associated genetic variation in the context of the 3D structure of the genome in the nucleus of disease-relevant immune cell types have implicated the kinase HIPK1 as a factor controlling SLE susceptibility. This kinase has been studied in the context of cancer, but a role for HIPK1 in immunity, tolerance, or SLE has not been explored. In this exploratory, high-risk/high- impact application we will use genetic and pharmacologic targeting approaches to establish whether HIPK1 regulates T cell differentiation, T cell-dependent humoral immune responses, and SLE pathophysiology in powerful human and mouse models of follicular lymphocyte differentiation and function. The outcome of these studies is likely to forward basic understanding of the regulation of humoral immunity and suggest a completely novel immunomodulatory approach for the management of SLE disease.

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