PHAGOCYTOSIS AND MERTK FAMILY OF THE RECEPTOR TYROSINE KINASE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 受体酪氨酸激酶家族参与先天和获得性免疫反应。缺乏这三种受体的小鼠表现出专业或非专业吞噬细胞对凋亡细胞或废弃细胞器的清除缺陷。凋亡细胞是自身抗原的主要来源，清除障碍导致自身免疫的发展。此外，AXL和MerTK是家族的两个成员，由巨噬细胞和树突状细胞表达，并在抗原提呈细胞激活过程中发挥负性调节作用。自身抗原在突变的APC中过度表达会导致自身免疫性疾病。我们之前已经证明，三重(以及AM双)突变会产生高水平的循环自身抗体，产生过度反应的眼部抗原特异性同基因T细胞群。在这一研究期间，我们进一步证明了AM双(也是三)突变小鼠通过Th1亚型T细胞的压倒性过度激活而患上了眼部自身免疫性疾病。这项研究使我们更接近了解人类葡萄膜炎的分子病因学。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The TAM family of receptor tyrosine kinases participates in both innate and adaptive immune response. Mice lacking all three receptors exhibit defective clearance of apoptotic cells or spent cellular organelles by the professional or non-professional phagocytes. Apoptotic cells are a major source of autoantigens and impaired clearance leads to the development of autoimmunity. Furthermore, Axl and Mertk, two members of TAM family, are expressed by macrophage and dendritic cells (DC), and play a negatively regulatory role during the antigen-presenting cell (APC) activation. Overpresentation of autoantigens in the mutant APCs causes autoimmune disorders. We have previously shown that TAM triple (as well as AM double) mutants produce elevated levels of circulating autoantibodies, overreactive ocular antigen-specific syngeneic T-cell population. In this period of study, we further demonstrated that AM double (also triple) mutant mice developed ocular autoimmune disorder through overwhelmingly hyperactivation of Th1 subtype of T cells. This study brings us even closer to understanding of the molecular etiology for human uveitis.