The Biology of Microglia: Adenosine A3 Receptor Suppression

小胶质细胞是存在于大脑和脊髓范围内的免疫细胞。以前人们认为小胶质细胞仅仅是神经元的支持细胞，但现在很清楚，小胶质细胞有许多重要的作用：它们是塑造发育和成熟神经系统细胞结构的雕刻家，是修改神经回路的电工，是保护大脑和脊髓的守护者。小胶质细胞是如何完成这些不同任务的，目前还不清楚。我的研究和培训计划侧重于了解小胶质细胞的基本生物学和控制这些细胞活动的核心过程。我们最近有一个令人兴奋的发现，小胶质细胞是由腺苷A3受体（A3R）调节的，这些受体控制着小胶质细胞的活性。这项拟议的研究剖析了A3R信号传导的基本步骤（螺母和螺栓），以及对小胶质细胞如何与其他细胞交流的影响。实验还将研究A3R控制转录因子Runx1活性的机制，以及驱动A3R介导的白介素-10（一种关键的小胶质细胞信号分子）释放的过程。我们将使用先进的生化，分子和成像方法来解构A3R如何控制小胶质细胞功能。这一新知识将对理解小胶质细胞的交流产生直接影响，并为更广泛地理解整个中枢神经系统的小胶质细胞生物学形成一个概念框架。这项拟议研究的核心是培养高素质的个人，他们将成为未来学术界、政府和工业界的领导者。

Microglia are immune cells that reside within the confines of the brain and spinal cord. Previously assumed to be merely support cells for neurons, it is now clear that microglia have many important roles: they are sculptors that shape the cellular architecture of the developing and mature nervous system, electricians that modify neuronal circuitry, and guardians that protect the brain and spinal cord. How microglia undertake these different tasks is not well understood. My research and training program focuses on understanding the fundamental biology of microglia and the core processes that control activity of these cells. We recently made the exciting discovery that microglia are regulated by adenosine A3 receptors (A3R) these receptors keep microglia activity in check. The proposed research dissects the essential steps in A3R signaling (the nuts and bolts') and the impact on how microglia communicate with other cells. Experiments will also examine the machinery by which A3R controls activity of the transcription factor Runx1 and the process that drives A3R-mediated release of interleukin-10, a key microglia signaling molecule. We will use advanced biochemical, molecular, and imaging approaches to deconstruct how A3R controls microglia function. This new knowledge will have direct implications for understanding microglia communication, and form a conceptual framework for broader understanding of microglia biology throughout the central nervous system. At the core of this proposed research is the training of highly qualified individuals who will become future leaders in academia, government, and industry.