Regulation and Function of Polarity and Asymmetric Cell Division in Immunity

描述（由申请方提供）：细胞极性对于包括迁移、不对称分裂和组织发育在内的多种过程至关重要。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质网络。细胞极性的调节和功能后果已经在模式生物如芽殖酵母、C. elegans和果蝇，但在哺乳动物细胞中还没有很好的理解。 在哺乳动物免疫系统中，T淋巴细胞在感染性攻击期间遇到携带微生物组分的抗原呈递细胞后经历实质性重组和极化。保守的极性复合物是经历重组的细胞组分之一，但它们如何调节T淋巴细胞命运的特化和功能仍然未知。该提议借鉴了细胞生物学、发育生物学和免疫学的不同学科，以检验细胞极性调节（1）效应T淋巴细胞亚群和记忆T淋巴细胞亚群从其幼稚前体的产生以及（2）效应T淋巴细胞功能的执行的假设。本文提出的目标的实现可能会产生重要的见解的基本机制，极性调节剂影响细胞命运的规范和功能，并可能有助于提供一个框架，合理的疫苗开发。 公共卫生相关性：效应和记忆T淋巴细胞是免疫系统的细胞，提供对微生物的保护。我们的目标是了解这些细胞是如何产生的，以及它们是如何发挥作用的。这些研究可能有助于我们改进疫苗。

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.