Regulation and Function of Polarity and Asymmetric Cell Division in Immunity

描述(申请人提供)：细胞极性对多种过程至关重要，包括迁移、不对称分裂和组织发育。细胞极性和不对称分裂的主要调节者之一是极性蛋白质网络，该网络在进化过程中是保守的。在发芽酵母、线虫和果蝇等模式生物中，细胞极性的调节和功能后果已经得到了很好的研究，但在哺乳动物细胞中还没有被很好地理解。在哺乳动物的免疫系统中，T淋巴细胞在感染挑战中遇到含有微生物成分的抗原提呈细胞后，会经历实质性的重组和极化。保守的极性复合体是经历重组的细胞成分之一，但它们如何调节T淋巴细胞命运的特性和功能仍不清楚。这一建议借鉴了细胞生物学、发育生物学和免疫学的不同学科来检验这样的假设，即细胞极性调节(1)来自其幼稚前辈的效应和记忆T淋巴细胞亚群的产生以及(2)效应T淋巴细胞功能的执行。本文提出的目标的实现可能会对极性调节因子影响细胞命运指定和功能的基本机制产生重要的见解，并可能有助于为疫苗的合理开发提供一个框架。

DESCRIPTION (provided by applicant): Cell polarity is critical for diverse processes including migration, asymmetric division, and tissue development. One of the major regulators of cell polarity and asymmetric division is a network of polarity proteins that has been conserved across evolution. The regulation and functional consequences of cell polarity have been well studied in model organisms such as budding yeast, C. elegans, and Drosophila, but are not well understood in mammalian cells. In the mammalian immune system, a T lymphocyte undergoes a substantial reorganization and polarization after encountering an antigen-presenting cell bearing microbial components during an infectious challenge. The conserved polarity complexes are among the cellular components that undergo reorganization, but how they regulate T lymphocyte fate specification and function remains unknown. This proposal draws from the disparate disciplines of cell biology, developmental biology, and immunology to test the hypothesis that cell polarity regulates (1) the generation of effector and memory T lymphocyte subsets from their naive predecessors as well as (2) the execution of effector T lymphocyte function. Accomplishment of the aims proposed herein is likely to yield important insights about the fundamental mechanisms by which regulators of polarity influence cell fate specification and function, and may help to provide a framework for the rational development of vaccines.