Core D - Immunopathology

核心摘要 此PPG应用程序的总体目标是从机理上理解蜂窝和 自身免疫、癌症和慢性疾病中PD1和LAG3相互作用调节T细胞功能的分子基础 病毒感染。核心D将为PPG调查人员提供尖端和相关的技术和专业知识 了解PD1和LAG3之间的相互作用如何影响细胞相互作用 自身免疫性疾病小鼠完整实验组织中的相关分子通路 (项目1)、癌症(项目2)和慢性病毒感染(项目3)。这一核心的目标是：目标1： 为详细的免疫病理组织分析提供基本的专业知识和技术；目标2：使用高度多重循环免疫荧光(TCyCIF)应用高分辨率定量相关免疫病理学；以及目标3：维护带注释的生物谱库/档案，以供未来研究。这些数据将 与Core C和PPG项目生成的数据接口，以便开发协议以可视化新的 分子，以及由传统组织学产生的指标(例如，定性评估和分级 病变严重程度)和临床参数(如存活率和体重减轻)。核心D将广泛与 所有三个项目，核心A负责监督和行政支助，核心C负责开发新的染色 核心C确定的关键基因及其产物的细胞和组织学研究方案是 受PD1和LAG3调控。

CORE SUMMARY The overall goal of this PPG application is to develop a mechanistic understanding of the cellular and molecular basis for PD1 and LAG3 interactions that regulate T cell function in autoimmunity, cancer and chronic viral infections. Core D will provide sophisticated and relevant technologies and expertise to PPG investigators for understanding how the interplay between PD1 and LAG3 affects cellular interactions and relevant molecular pathways in intact experimental tissues from mice with autoimmune disease (Project 1), cancer (Project 2) and chronic viral infection (Project 3). The Aims of this Core are: AIM 1: To provide basic expertise and technologies for detailed immunopathologic tissue analysis; AIM 2: To apply highresolution quantitative, correlative immunopathology using highly-multiplexed cyclic immunofluorescence (tCyCIF); and AIM 3: To maintain an annotated biospecimen bank/archive for future studies. These data will interface with data generated by Core C and PPG projects in order to develop protocols to visualize new molecules, as well as metrics generated from conventional histology (e.g., qualitative assessment and grading of lesion severity) and clinical parameters (e.g. survival and weight loss). Core D will interact extensively with all three Projects, with Core A for oversight and administrative support, and Core C by developing new staining protocols for cellular and histologic investigation of key genes and their products that Core C determines are regulated by PD1 and LAG3.