Role and Regulation of BLIMP-1 in Myeloid Cells

描述（由申请人提供）：髓系细胞起关键作用 在先天免疫和适应性免疫中的作用。此应用程序旨在 阐明B的作用、分子作用机制和调控 髓系细胞中的淋巴细胞诱导成熟蛋白-1（Blimp-1）。 Blimp-1是一种含锌指的转录抑制因子，已知其 在B淋巴细胞向血浆的定向和分化中起关键作用 细胞然而，我们最近的研究表明，Blimp-1也在细胞中表达 单核细胞和粒细胞，并诱导巨噬细胞分化 早幼粒细胞系和初级骨髓祖细胞。再者是 需要并足以触发U937的巨噬细胞分化 前单核细胞因此，Blimp-1可能是一个关键的调节器， 巨噬细胞的分化和功能，也可能是重要的 其他髓系细胞的分化和/或功能。 该项目有三个具体目标。首先，我们将使用基因靶向， Blimp-1的抑制形式的表达以确定髓样细胞的能力。 细胞在缺乏Blimp-1的情况下分化和发挥功能。这些研究 旨在确定BLIMP-1在巨噬细胞、粒细胞和 髓样树突细胞其次，我们将利用微阵列技术， 表征Blimp-1依赖的巨噬细胞过程中的基因表达程序 和粒细胞分化。将进行进一步研究，以确定 Blimp-1的直接靶点，并在髓系和B淋巴细胞中进行比较 血统最后，负责调控的信号和机制 将研究骨髓细胞中的Blimp-1表达。

DESCRIPTION (provided by applicant): Cells of the myeloid lineage play critical roles in both innate and adaptive immunity. This application is designed to elucidate the role, molecular mechanism of action and regulation of B Lymphocyte Induced Maturation Protein-1 (Blimp-1) in myeloid lineage cells. Blimp-1 is a zinc finger-containing transcriptional repressor that is known to play a key role in commitment and differentiation of B lymphocytes to plasma cells. However, our recent studies have shown that Blimp-1 is also expressed in monocytes and granulocytes and induced upon macrophage differentiation of promyeloid lines and primary bone marrow progenitors. Furthermore, it is required and sufficient to trigger macrophage differentiation of U937 promonocytes. Therefore, Blimp-1 is likely to be a critical regulator of macrophage differentiation and function and may also be important for the differentiation and/or function of other myeloid lineage cells. The project has three specific aims. First, we will use gene targeting and expression of inhibitory forms of Blimp-1 to determine the ability of myeloid cells to differentiate and function in the absence of Blimp-1. These studies are designed to establish the role of BLIMP-1 in macrophages, granulocytes and myeloid dentritic cells. Second, we will exploit microarray technology to characterize Blimp-1 -dependent programs of gene expression during macrophage and granulocyte differentiation. Further studies will be performed to identify direct targets of Blimp-1 and to compare them among myeloid and B lymphocyte lineages. Finally, the signals and mechanisms responsible for regulation of Blimp-1 expression in myeloid cells will be studied.