Core C TEST IT

核心 C 测试

基本信息

批准号：
10455749
负责人：
I. Caroline Le Poole
金额：
$ 18.09万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-20 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10455749
关键词：
3-Dimensional Affect Antibodies Antigens Area Biological Assay Biology Blood Cell model Cells Clinical Clinical Research Code Collaborations Communities Cutaneous Data Dermatology Development Disease Drug or chemical Tissue Distribution Engineered Gene Engineered skin Engineering Environment Equipment Exposure to Faculty Flow Cytometry Goals Grant Health Homeostasis Human Hypersensitivity skin testing Image Immune Immune response Immune system Immunologic Monitoring Immunological Models Immunologics Immunology Immunotherapeutic agent In Situ In Vitro Individual Inflammation Innate Immune System Institutional Review Boards Instruction Investigation Laboratories Lead Manuals Monitor Morphology Mus Nanotechnology Nucleotides Pharmaceutical Preparations Preparation Protocols documentation Records Research Research Personnel Research Training Resources Safety Sampling Scientist Secure Services Skin Skin Tissue Technology Testing Tissue Engineering Tissues Translational Research Ultraviolet Rays Universities base biobank design environmental agent enzyme linked immunospot assay equipment training experimental study gene product genetic manipulation graduate student healthy volunteer in vivo in vivo monitoring interest keratinocyte learning materials liquid crystal polymer novel programs reconstitution reconstruction repository sample archive skin disorder tissue archive transcriptome sequencing translational study ultraviolet

项目摘要

The skin forms a primary interface with the environment, with the keratinocyte a critical component of the innate immune system. Perturbation of healthy skin can lead to inflammation through cutaneous immune responses. As such, the immunology of skin is an important focus of a SBDRC with “The Keratinocyte and its Microenvironment” as its theme. he skin immune system entails an interactive set of innate and adaptive immune cells that can be studied in situ, taken apart for studies at the single cell level, or reconstructed to recreate immune conditions of the skin. The objective of the Translational and Experimental Skin Testing and Immune Tracing (TEST IT) Core is to support and promote the research of SBDRC scientists interested in human and murine cutaneous immune responses in health and disease. The Core will isolate various immune cells from healthy and diseased skin, including at the single cell level, and offer preparative services for the characterization of these cells directly or in functional assays. Using Vectra multispectral imaging equipment, the Core will assist in designing experiments allowing in situ monitoring of human and mouse skin samples, explants and engineered skin. The Core will provide guidance for the efficient expansion of immune cells from skin and blood to be recombined with 3D reconstituted human skin or explants by the Skin Tissue Engineering and Morphology (STEM Core). Prior to reconstruction, cells can be genetically manipulated with products from the Gene Engineering, Transduction and Nanotechnology (GET iN) Core. These engineered keratinocyte-immune cell models will then be available for further immune assessment. A unique and highly novel aspect of the TEST IT core will be to provide a skin challenge facility for in vivo monitoring. This will be accomplished through a dedicated clinical unit and staff to test exposure to environmental agents that affect skin immunologically, whether in a potentially deleterious way, such as ultraviolet/UV light, or in a beneficial way, such as topical medications that suppress immune responses. The Core will oversee the Tissue Acquisition Program (TAP), which obtains archival samples, as well as fresh skin, blood, and other samples (including through the in vivo skin challenge facility) for a central biorepository with secure records; coded, deidentified tissues are distributed to scientists for use in individual laboratories or the service Cores. The Core will also maintain a roster of healthy volunteers and individuals with skin disease who are willing to participate in IRB-approved, skin challenge experiments. These translational studies support mechanistic investigations and provide proof-of-concept data. The Core also focuses on training the research community about immunodermatology, offering expertise in designing mouse and human experiments involving the skin immune system and generating course material in immunodermatology, immunotherapeutics, and immune monitoring. This is a novel core that focuses on enabling investigators to perform advanced and highly translational immune skin research. The ability to study perturbed human skin in a controlled manner will greatly facilitate translational research.

皮肤形成与环境的主要界面，角质形成细胞是先天皮肤的关键组成部分。健康皮肤的干扰会通过皮肤免疫反应导致炎症。因此，皮肤免疫学是 SBDRC 的一个重要焦点，其主题为“角质形成细胞及其其主题是“微环境”，皮肤免疫系统需要一组相互作用的先天免疫和适应性免疫。可以进行原位研究、拆开进行单细胞水平研究或重建以重新创建的细胞皮肤的免疫状况。转化和实验皮肤测试和免疫的目的。追踪（TEST IT）核心是支持和促进 SBDRC 科学家对人类和健康和疾病状态下的小鼠皮肤免疫反应，核心将从中分离出各种免疫细胞。健康和患病的皮肤，包括单细胞水平，并提供表征准备服务 Core 将直接或使用 Vectra 多光谱成像设备对这些细胞进行协助。设计实验，允许对人类和小鼠皮肤样本、外植体和工程样品进行原位监测核心将为皮肤和血液中免疫细胞的有效扩增提供指导。通过皮肤组织工程和形态学与 3D 重建人体皮肤或外植体重组（STEM 核心）在重建之前，可以使用基因产品对细胞进行基因操作。工程、转导和纳米技术 (GET iN) 核心。然后模型将可用于进一步的免疫评估，这是 TEST IT 的一个独特且高度新颖的方面。核心是提供用于体内监测的皮肤挑战设施，这将通过一个来完成。专门的临床单位和工作人员测试接触影响皮肤免疫的环境因素，无论是以潜在有害的方式，例如紫外线/紫外线，还是以有益的方式，例如局部使用抑制免疫反应的药物。核心将监督组织获取计划（TAP），它获取档案样本以及新鲜皮肤、血液和其他样本（包括通过体内皮肤挑战设施）用于分配安全记录的中央生物储存库；供各个实验室或服务核心使用的科学家，核心也将维护一个健康的名册。愿意参加 IRB 批准的皮肤挑战的志愿者和患有皮肤病的个人这些转化研究支持机制研究并提供概念验证数据。该核心还专注于对免疫皮肤病学研究界进行培训，提供以下方面的专业知识：设计涉及皮肤免疫系统的小鼠和人体实验并生成课程材料免疫皮肤病学、免疫治疗和免疫监测是一个专注于实现的新型核心。研究人员进行先进和高度转化的免疫皮肤研究的能力。以受控方式进行人类皮肤将极大地促进转化研究。