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

描述（由申请人提供）：系统性狼疮（SLE）是一种自身免疫性疾病，其特征是产生一系列抗核抗体，女性比男性更常见。在SLE小鼠模型中，B细胞和T细胞功能异常已被广泛研究。我们培育了一种树突细胞中缺失Blimp-1功能的小鼠。雌性小鼠会产生类似狼疮的血清学，而雄性小鼠则不会。我们建议了解树突状细胞功能的改变和随后的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仅在雌性小鼠中表现为自身免疫。这些研究将进一步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。

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.