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

总结 新型冠状病毒SARS-CoV-2导致COVID-19大流行。病毒通过 呼吸道虽然大多数COVID-19患者没有表现出或表现出轻微的临床症状， 百分之发展严重的免疫介导的病理并发症，这可能会导致伤害 以及肺和各种重要器官的衰竭，并占COVID-19死亡人数的大多数。 了解免疫系统的不同组成部分如何参与病毒控制， 病理发展对于我们理解疾病的发病机制至关重要， 制定预防和治疗策略。在这份拨款申请中，我们打算解剖 CCR 10调节的粘膜伊加抗体应答参与SARS-CoV-2感染清除 与使用小鼠模型在两个特定目的中的免疫病理学发展相比。在目标1中，我们 将确定SARS-CoV-2感染中CCR 10调节的原发性粘膜伊加应答的作用 清除和免疫病理学发展。在目标2中，我们将确定CCR 10的作用- SARS-CoV-2感染和免疫病理中调节的记忆性粘膜伊加应答 发展我们建议的研究结果不仅有助于我们了解参与 粘膜伊加反应在清除病毒感染和COVID-19发病机制中的作用， 为未来疫苗接种策略的发展提供指导，以诱导适当的伊加反应， 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.