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：
10622551
负责人：
YAN XIANG
金额：
$ 19.38万
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 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10622551
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 Maintenance Mediating Memory Memory B-Lymphocyte Modified Vaccinia Virus Ankara Mucous Membrane Mus Nucleocapsid Nucleocapsid Proteins Organ Pathogenesis Pathologic Patients Proteins Recombinants Regulation 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 chemokine receptor disorder prevention enhanced green fluorescent protein immunopathology lung failure 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.

概括新型冠状病毒 SARS-CoV-2 导致了 COVID-19 大流行。病毒通过以下途径感染呼吸道。虽然大多数 COVID-19 患者没有表现出临床症状或表现出轻微的临床症状，但一小部分患者百分比出现严重的免疫介导的病理并发症，这可能导致受伤肺和各种重要器官的衰竭是导致 COVID-19 死亡的主要原因。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了解疾病的发病机制至关重要制定预防和治疗策略。在此拨款申请中，我们建议剖析 CCR10 调节的粘膜 IgA 抗体反应参与 SARS-CoV-2 感染清除与使用小鼠模型在两个特定目标中的免疫病理学发展进行比较。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学发展。在目标 2 中，我们将确定 CCR10 的作用—— SARS-CoV-2 感染和免疫病理学中调节记忆粘膜 IgA 反应发展。我们提出的研究结果不仅有助于我们了解参与粘膜 IgA 反应在清除病毒感染和 COVID-19 发病机制中的作用为未来制定疫苗接种策略提供指导，以诱导适当的 IgA 反应疾病预防。