Regulation and Function of Polarity and Asymmetric Cell Division in Immunity

描述（由申请人提供）：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因子之一是在进化过程中保守的极性蛋白网络。细胞极性的调控和功能后果已经在模式生物中得到了很好的研究，如出芽酵母、秀丽隐杆线虫和果蝇，但在哺乳动物细胞中还没有得到很好的了解。在哺乳动物免疫系统中，T淋巴细胞在感染挑战中遇到携带微生物成分的抗原呈递细胞后，经历了大量的重组和极化。保守极性复合物是经历重组的细胞成分之一，但它们如何调节T淋巴细胞的命运、规范和功能尚不清楚。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，以验证细胞极性调节(1)效应T淋巴细胞亚群和记忆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的假设。实现本文提出的目标可能会对极性调节因子影响细胞命运、规格和功能的基本机制产生重要见解，并可能有助于为合理开发疫苗提供框架。

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. PUBLIC HEALTH RELEVANCE: Effector and memory T lymphocytes are cells of the immune system that provide protection against microbes. Our goal is to understand how these cells are generated and how they function. These studies may help our efforts to improve vaccines.