Fc gamma Receptors & Herpes Stromal Keratitis

描述（由申请方提供）：我们实验室的既往研究表明，HSV-1角膜感染后给予的低剂量单克隆抗体被动转移至病毒糖蛋白可预防永久性致盲性角膜炎症的形成。抗体如何发挥其保护作用尚不清楚。然而，由于当病毒中和F（ab）2时未观察到保护作用，因此给予片段代替完整抗体Fc γ受体（Fc γ R）。最近的进展导致了对Fc γ R的重要性的根本性修订。现在已经认识到两种类型-当连接时激活细胞的类型和抑制细胞激活的类型。当两种类型由同一细胞表达时，认为由共连接触发的净细胞应答取决于两种相反信号的表达比率。我们将使用野生型和FcgR基因敲除小鼠来测试病毒抗原：抗体复合物通过共连接有利于负FcgR信号传导，从而抑制疱疹性基质角膜炎发展的前提。我们的研究将提供有关FcgammaRs在眼组织中的表达和功能的新信息，并可能导致控制角膜炎症的新策略。

DESCRIPTION (provided by applicant): Prior studies in our laboratory have demonstrated that passive transfer of low dose monoclonal antibody to viral glycoproteins given after HSV-1 corneal infection can prevent the establishment of permanent blinding corneal inflammation. How antibody exerts its protective effect is not known. However, since no protection was seen when virus neutralizing F(ab)2, fragments were given in place of intact antibody Fc gamma receptors (FcgammaRs) were though to be involved. Recent advances have led to a fundamental revision of the significance of FcgammaRs. Two types are now recognized - those that when ligated activate cells and those which inhibit cell activation. Where both types are expressed by the same cell the net cellular response triggered by co-ligation is thought to depend on the ratio of expression of the two opposing signals. We will use wildtype and FcgR gene knockout mice to test the premise that viral antigen:antibody complexes via co-ligation favor negative FcgR signaling, and so suppress herpes stromal keratitis development. Our studies will provide new information on the expression and function of FcgammaRs in ocular tissue and may lead to novel strategies for controlling corneal inflammation.