INTESTINAL IMMUNE SYSTEM IN HOST-ENVIRONMENT INTERACTION

宿主与环境相互作用中的肠道免疫系统

• 批准号: 8011407
• 负责人: Martin Frederick KAGNOFF
• 金额: $ 10.05万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8011407
• 关键词: Address; Adjuvant; Animal Model; Biological Models; Cell Line; Cell Separation; Cell physiology; Cells; Cholera Toxin; Colon; Communication; Dendritic Cells; Disease; Enteral; Environment; Epithelial Cells; Equilibrium; Funding; Gastroenterology; Giardia; Goals; Granulocyte-Macrophage Colony-Stimulating Factor; Guidelines; Histopathology; Homeostasis; Hypersensitivity; Image; Immune; Immune response; Immune system; Immunity; Immunology; In Vitro; Infection; Inflammatory; Inflammatory Response; Institutes; Intestinal Mucosa; Intestines; Lesion; Link; Medicine; Microbe; Modeling; Molecular; Mucosal Immune Responses; Mucositis; Mus; National Institute of Diabetes and Digestive and Kidney Diseases; Nature; Neurosciences; Outcome; Pathogenesis; Pathology; Regulation; Regulatory T-Lymphocyte; Research; Research Personnel; Research Project Grants; Retinoids; Rheumatology; Rotavirus; Signal Pathway; Signal Transduction; Small Intestines; Small intestine mucous membrane; T-Lymphocyte; Work; acquired immunity; base; enteric pathogen; experience; improved; in vivo; interdisciplinary approach; medical schools; microbial; minimally invasive; mouse model; novel; pathogen; programs; response; therapeutic target

DESCRIPTION, OVERALL (provided by applicant): The central theme of the Program Project Is focused on mechanisms that determine innate and acquired immune responses in the intestinal mucosa to enteric microbes and microbial products, and the consequent mucosal protective immune and inflammatory responses. The four interrelated research projects specifically address the regulation of communication between epithelial cells and dendritic cells, and between dendritic cells and T cells, which takes place during mucosal homeostasis and protective immunity. Model enteric pathogens are used to probe mucosal cellular responses in novel in vivo and in vitro murine model systems. The program brings together experienced investigators from the Departments of Medicine, Pathology, and Neurosciences and the UCSD campus based La Jolla Institute for Allergy and Immunology. The investigators have a record of significant expertise in cellular and molecular mucosal immunology, mucosal inflammation, cell signaling and microbial pathogenesis, and a record of collaborative interactions. Research Unit 1 investigates the regulation of innate mucosal immune responses by dendritic cells (DC) and epithelial cells in the colon and small intestine. Unit 1 uses an attaching and effacing lesion-inducing enteric pathogen and rotavirus to probe the host response, and the mechanisms by which granulocyte-macrophage colony stimulating factor determines the outcome of enteric infection. Research Unit 2 investigates intestinal mucosal responses that determine immune defenses against minimally invasive enteric pathogens, using Giardia as a model protozoan pathogen that elicits strong protective immunity in the absence of mucosal inflammation. Research Unit 3 investigates how mucosal adjuvants override the tolerance-inducing effects of T regulatory cells and provoke effector T cell immune responses, with a focus on cholera toxin and Th17 differentiation in vitro and in vivo. Research Unit 4, which is new to the Program with the renewal application, investigates mechanisms by which retinoids determine the balance between normal mucosal homeostasis and protective immunity through their activity on DC and T cells. The research projects are supported by four Cores: a Mouse Model Core, a Histopathology Core, an Imaging and Cell Sorting Core and an Administrative Core.

总体描述（由申请人提供）：