HIPK1: a new immunomodulatory target for SLE

摘要 我们先前的工作使用系统性红斑狼疮（SLE）相关遗传变异的物理图谱， 疾病相关免疫细胞类型的细胞核中基因组的3D结构的背景已经暗示了 激酶HIPK 1作为控制SLE易感性的因素。这种激酶已经在癌症的背景下进行了研究， 但HIPK 1在免疫、耐受或SLE中的作用尚未被探索。在这个探索性的，高风险/高- 影响应用，我们将使用遗传和药理学靶向方法来确定HIPK 1 调节T细胞分化、T细胞依赖性体液免疫应答和SLE病理生理学， 强大的人类和小鼠滤泡淋巴细胞分化和功能模型。成果的 研究可能会促进对体液免疫调节的基本理解，并提出一个完整的 新的免疫调节方法用于SLE疾病的管理。

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.