Roles of CCR10 in regulation of IgA responses to SARS-CoV-2 infection

摘要 新型冠状病毒SARS-CoV-2导致新冠肺炎大流行。该病毒通过 呼吸道。虽然大多数新冠肺炎患者没有临床症状或症状轻微，但一小部分患者 出现严重的免疫介导的病理并发症的百分比，这可能导致伤害 以及肺和各种重要器官的衰竭，占新冠肺炎死亡的大部分。 了解免疫系统的不同组成部分如何参与病毒控制和 病理发展对于我们理解该病的发病机制和 制定预防和治疗策略。在这项拨款申请中，我们建议剖析 CCR10调节的黏膜IgA抗体应答参与SARS-CoV-2感染清除 在两个特定的目标中，对比使用小鼠模型的免疫病理发展。在目标1中，我们 将确定CCR10调节的初级粘膜IgA反应在SARS-CoV-2感染中的作用 清除和免疫病理发展。在目标2中，我们将确定CCR10的作用- SARS-CoV-2感染中的记忆调节黏膜IgA反应与免疫病理 发展。我们建议的研究结果不仅将有助于我们对参与 黏膜免疫球蛋白A在清除病毒感染和新冠肺炎发病机制中的作用 就疫苗接种策略的未来发展提供指南，以诱导适当的免疫球蛋白A反应 疾病预防。

Summary The novel coronavirus SARS-CoV-2 causes the COVID-19 pandemic. The virus infects through the respiratory tracts. While most COVID-19 patients display no or mild clinical symptoms, a small percentage develop severe immune-mediated pathological complications, which could lead to injury and failure of the lung and various important organs and account for the majority of COVID-19 deaths. Understanding how different components of the immune system are involved in the viral control and pathological development is crucial for our understanding of pathogenesis of the disease and developing preventative and therapeutic strategies. In this grant application, we propose to dissect involvement of CCR10-regulated mucosal IgA antibody responses in SARS-CoV-2 infection clearance versus immune-pathological development using mouse models in two specific aims. In the Aim 1, we will determine the role of CCR10-regulated primary mucosal IgA responses in SARS-CoV-2-infection clearance and immunopathological development. In the Aim 2, we will determine the role of CCR10- regulated memory mucosal IgA responses in SARS-CoV-2 infection and immune-pathological development. The findings of our proposed study will not only help our understanding of involvement of mucosal IgA responses in clearance of the viral infection and pathogenesis of COVID-19 but also provide a guide on future development of vaccination strategies to induce proper IgA response for the disease prevention.