Opposing roles of TLR 2 and TLR 4 in non-infectious lung injury

描述(由申请人提供)：先天免疫系统在肺纤维化中的作用仍不完全清楚。在其他系统中，先天免疫系统的组成部分形成了适应性免疫系统更精确的反应。利用一个描述良好的亚急性肺部炎症和纤维化的动物模型，将检验两种Toll样受体的作用，这两种受体是先天免疫系统的主要成分，以及每种受体对T淋巴细胞分化的特定影响。具体地说，目标1将描述TLR2在使T细胞远离保护性Th1发育途径方面的作用，而特定目标2将展示TLR4在产生保护肺损伤的T调节细胞方面的作用。肺纤维化是多种疾病的终末期，可导致进行性呼吸衰竭和死亡。目前对这种情况发生的原因以及如何阻止这一过程的了解非常有限，更好的理解将有助于更有效的治疗。

DESCRIPTION (provided by applicant): The role of the innate immune system in pulmonary fibrosis, remains imperfectly understood. In other systems it is established that components of the innate immune system shape the more precise response of the adaptive immune system. Using a well described animal model of subacute pulmonary inflammation and fibrosis, the role of two of the Toll-Like Receptors, major components of the innate immune sytem and the specific influence each has on T lymphocyte differentiation, will be examined. Specifically, Aim 1 will describe the role of TLR2 in turning T cells away from a protective Th1 pathway of development, and Specific Aim 2 will demonstrate the role of TLR4 in producing T regulatory cells that protect from lung injury. Pulmonary fibrosis is the end stage of a wide range of diverse diseases, and leads to progressive respiratory failure and death. Currently understanding of why this occurs, and how to stop this process, is very limited, and better understanding will allow more useful therapies.