权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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

CCR10 在调节 SARS-CoV-2 感染 IgA 反应中的作用

基本信息

批准号：
10442019
负责人：
YAN XIANG
金额：
$ 23.25万
依托单位：
UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-05-16 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10442019
关键词：
2019-nCoV Antibodies Antibody Response Antibody titer measurement Applications Grants B-Lymphocytes COVID-19 mortality COVID-19 pandemic COVID-19 pathogenesis COVID-19 patient COVID-19 vaccine Cells Cessation of life Clinical Code Development Developmental Process Disease Future GPR2 gene Homing Immune Immune response Immune system Immunize Immunoglobulin A Immunoglobulin-Secreting Cells Infection Infection Control Infection prevention Injury Invaded Knock-in Mouse Knock-out Knockout Mice Lead Maintenance Mediating Memory Memory B-Lymphocyte Modified Vaccinia Virus Ankara Mucous Membrane Mus Nucleocapsid Nucleocapsid Proteins Organ Pathogenesis Pathologic Patients Proteins Recombinants Regulation Respiratory Failure Respiratory System Role Route SARS-CoV-2 infection SARS-CoV-2 pathogenesis SARS-CoV-2 spike protein Severities Site Symptoms Therapeutic Tissues Viral Viral Pathogenesis Virus Virus Diseases base chemokine receptor disorder prevention enhanced green fluorescent protein immunopathology migration mouse model mucosa-associated lymphoid tissue mucosal site novel coronavirus pathogen response vaccination strategy

项目摘要

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.

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。