The role of E2-2 in the development and function of plasmacytoid dendritic cells

描述（申请人提供）：浆细胞样树突状细胞（pDC）代表一种独特的免疫细胞谱系，在抗病毒的先天免疫应答中发挥重要作用。pDC识别病毒相关核酸并通过快速分泌大量的I型干扰素（IFN）来应答，因此它们的另一个名称为：I型干扰素产生细胞（IPC）。pDC还可以在活化后分化成能够将抗原呈递给免疫系统的适应性臂的常规树突细胞。因此，pDC对于身体控制病毒感染至关重要。另一方面，异常pDC过度活跃与自身免疫性疾病如银屑病和系统性红斑狼疮中I型IFN水平的增加有关。因此，pDC在正常和异常免疫应答中发挥重要作用，并在一些疾病的治疗中代表潜在的有用靶标。pDC具有独特的细胞和分子特征以及基因表达谱，使它们能够直接识别病毒，分泌大量的I型IFN，并分化为常规的树突状细胞。在过去的几年中，pDC的这些分子和细胞特征已经得到了很好的表征;然而，pDC谱系定型、成熟和功能的遗传基础仍然知之甚少。本课题的总体目标是研究碱性螺旋-环-螺旋转录因子在pDC发育和功能中的作用，并阐明这些转录因子在pDC中调控的途径。公共卫生相关性：这些研究将使我们深入了解控制pDC发育和功能的遗传网络，并可能为开发治疗病毒感染和某些自身免疫性疾病的新方法铺平道路。

DESCRIPTION (provided by applicant): Plasmacytoid dendritic cells (pDCs) represent a unique immune cell lineage that plays an essential role in innate immune responses against viruses. pDCs recognize virus-associated nucleic acids and respond by rapidly secreting massive amounts of type I interferons (IFN), hence their other name: type I interferon- producing cells (IPCs). pDCs can also differentiate, upon activation, into conventional dendritic cells that are capable of presenting antigens to the adaptive arm of the immune system. Thus, pDC are critical for the body's control of viral infections. On the other hand, abnormal pDC hyperactivity has been associated with increased type I IFN levels in autoimmune diseases such as psoriasis and systemic lupus erythematosus. Therefore, pDCs do play important roles in both normal and aberrant immune responses and represent potential useful targets in the treatment of some diseases. pDCs possess unique cellular and molecular characteristics and gene expression profiles that enable them to directly recognize viruses, secrete massive amounts of type I IFN, and differentiate into conventional dendritic cells. Over the last few years, these molecular and cellular features of pDCs have been well characterized; however, the genetic basis of pDC lineage commitment, maturation, and function still remains poorly understood. The overall objective of our research project is to study the role of basic helix-loop-helix transcription factors in the development and function pDCs, and elucidate the pathways that these transcription factors control in pDCs. PUBLIC HEALTH RELEVANCE: These studies will give us insights into the genetic network which controls the development and function of pDC, and may pave the way for the development of new approaches in the treatment of viral infections and some autoimmune disease.