Immunogenetic Mechanisms of Experimental Crohn's Disease

实验性克罗恩病的免疫遗传学机制

基本信息

批准号：
7364042
负责人：
Fabio Cominelli
金额：
$ 3.48万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-01-01 至 2010-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7364042
关键词：
AKR/J Mouse Acute Address Adhesions Administrator Adoptive Transfer Affect Age Agonist Animal Model Animals Anti-Inflammatory Agents Anti-inflammatory Antigens Apical Apoptosis Appendix Appointment Architecture Area Arts Attention Autoimmune Process Award B-Lymphocytes Backcrossings Basic Science Biliary Biological Biology Biomedical Engineering Bone Marrow Bone Marrow Transplantation Breeding Brothers CCR9 gene CD4 Positive T Lymphocytes Cancer Center Candidate Disease Gene Cardiovascular system Cell Adhesion Cell Adhesion Molecules Cell Lineage Cell physiology Cells Centers of Research Excellence Characteristics Chimera organism Chronic Chronic Inflammatory Infiltrate Chronic Phase Clinic Clinical Clinical Research Clinical Services Collaborations Collagen Communication Comparative Pathology Complex Condition Congenic Mice Congenic Strain Consultations Contraceptive Agents Core Facility Crohn&apos s disease Cytokine Gene Data Defect Defensins Deposition Development Diabetes Mellitus Digestive System Disorders Discipline Disease Disease Resistance Disease model Disease susceptibility Distal part of ileum Doctor of Philosophy Educational process of instructing Educational workshop Electronic Mail Endocrinology Endothelial Cells Ensure Environment Environmental Risk Factor Enzymes Epithelial Epithelial Cells Epithelium Equipment Etiology Event Exhibits Experimental Models Faculty Fee-for-Service Plans Feedback Fistula Fostering Foundations Functional disorder Funding Funding Mechanisms Future Gastric Juice Gastroenterology Gastrointestinal Diseases Gastrointestinal tract structure Gene Chips Gene Deletion Generations Genes Genetic Genetic Polymorphism Genetic Predisposition to Disease Germ Cells Germ-Free Goals Grant Granulomatous Growth Growth Factor Guidelines Head Health Health Services Research Helicobacter Hematopoietic Hepatology Histology Home environment Homing Human Human Resources Hunger Hydrochloric Acid Hyperplasia Hypertrophy Ileitis Image Imaging Techniques Immune Immune response Immune system Immunity Immunogenetics Immunology Immunosuppressive Agents In Vitro Inbred AKR Mice Inbred Strains Mice Individual Infectious Disease Immunology Inflammation Inflammatory Inflammatory Bowel Diseases Inflammatory Response Inflammatory disease of the intestine Integrins Intercellular adhesion molecule 1 Interdisciplinary Study Interleukin-10 Interleukin-12 Interleukin-13 Interleukin-2 Interleukin-4 Interleukin-5 International Intestines Investigation Investments Japan K-Series Research Career Programs Knock-out Knowledge L-Selectin Laboratories Lamina Propria Lead Lesion Leukocyte Trafficking Leukocytes Ligands Link Longevity Lymphocyte Manuscripts Maps Marshal Mediating Mediator of activation protein Medical Education Medical center Medicine Memory Mentors Mentorship Messenger RNA Methodology Microbiology Microbubbles Minority Mission Modeling Molds Molecular Molecular Biology Molecular Biology Techniques Molecular Genetics Monoclonal Antibodies Monoclonal Antibody Therapy Morphology Mouse Strains Mucosal Immunity Mucous Membrane Mus Myeloid Cells NCI Center for Cancer Research Names Natural Immunity Nature Nomenclature Numbers Operative Surgical Procedures P-Selectin P-selectin ligand protein PNAd Pancreas Paneth Cells Participant Partner in relationship Pathogenesis Pathologist Pathology Pathway interactions Patients Penetrance Peptic Ulcer Peptides Permeability Phenotype Physicians Play Polymerase Chain Reaction Population Positioning Attribute Postdoctoral Fellow Predisposition Preparation Principal Investigator Process Production Progress Reports Proteins Publications Published Comment Publishing Purpose Quality Control Radiology Specialty Range Recombinants Recruitment Activity Regulation Relapse Relative (related person)Research Research Design Research Infrastructure Research Personnel Research Project Grants Resource Development Resources Reverse Transcriptase Polymerase Chain Reaction Role Role playing therapy Running Schedule Scientist Score Services Severities Severity of illness Signal Transduction Sister Skin Small Interfering RNA Source Speed Steroids Structure Students Subgroup Submucosa Suggestion Susceptibility Gene System T-Cell Activation T-Lymphocyte TNF gene Techniques Technology Terminal Ileitis Testing Therapeutic Therapeutic Studies Tight Junctions Time Tissues Tokyo Training Training Programs Translational Research Transplantation Ulcerative Colitis United States United States National Institutes of Health Universities Upper arm Vascular Cell Adhesion Molecule-1 Virginia Week Woman Wood material Work anakinra animal facility base biodefense career cell type chemokine clinical phenotype concept congenic consomic cost cytokine design discount enteritis experience foot gastrointestinal genetic linkage analysis human disease ileum immune function improved in vivo innovation interest interleukin-23 intestinal epithelium laser capture microdissection malignant stomach neoplasm medical specialties member mouse model mucosal addressin cell adhesion molecule-1 multidisciplinary neutrophil novel novel therapeutics nutrition organizational structure professor programs prototype relating to nervous system reproductive research study response response to injury senescence stem cell fate structural biology success therapeutic target tool trafficking

项目摘要

DESCRIPTION (provided by applicant): Crohn's disease (CD) is a debilitating chronic condition with no known cure. Although there is evidence for the involvement of genetic, immunological, and environmental mechanisms, the precise cause(s) of CD remain unclear. Indirect evidence suggest that CD may be initiated by a dysregulated innate immune response against an "unknown" antigen in a genetically susceptible host. The major strengths of this competitive renewal are the unique SAMP1/YitFc (SAMP) mouse model, which has been extensively characterized by our group during the last funding period, and the highly synergistic nature of the program. The overall objective of this continuation proposal is to investigate the key pathogenic mechanisms underlying this spontaneous murine model of CD. The Program Project will continue to be directed by Dr. Fabio Cominell, and will consist of 5 projects and 2 cores. Project 1, headed by Dr. Cominelli, will extend its focus on the role of pivotal cytokines in mediating chronic intestinal inflammation in this model. Project 2, headed by Dr. Marcia McDuffie, will identify susceptibility genes involved in the predisposition to ileitis in SAMP mice based on the chromosomal loci identified during the previous funding period. Project 3, headed by Dr. Steven Cohn, will investigate the role of Paneth cells and their defensins in initiating ileitis. Project 4, headed by Dr. Klaus Ley, will study the mechanisms of lymphocyte homing and trafficking in SAMP mice, with a particular focus on L-selectin and PSGL-1. Project 5, a new project headed by Dr. Theresa Pizarro, will investigate the role of epithelial innate immune responses in initiating and perpetuating ileitis in SAMP mice. This Program is supported by an Administrative Core, which coordinates the program, and an Animal Core, which centralizes the production and breeding of SAMP mice and other congenic lines. The long-term goal of this Program Project is to understand the key pathogenic mechanisms of experimental CD, to aid development of a cure for at least a subgroup of patients with this devastating disease.

描述（由申请人提供）：克罗恩病 (CD) 是一种使人衰弱的慢性疾病，目前尚无治愈方法。尽管有证据表明遗传、免疫和环境机制参与其中，但 CD 的确切病因仍不清楚。间接证据表明，CD 可能是由遗传易感宿主体内针对“未知”抗原的先天免疫反应失调引发的。这一竞争性更新的主要优势是独特的 SAMP1/YitFc (SAMP) 小鼠模型，该模型在上一次资助期间已被我们小组广泛表征，以及该计划的高度协同性质。该延续提案的总体目标是研究这种自发性 CD 小鼠模型的关键致病机制。该计划项目将继续由 Fabio Cominell 博士指导，并将由 5 个项目和 2 个核心组成。由 Cominelli 博士领导的项目 1 将重点关注关键细胞因子在介导该模型中慢性肠道炎症中的作用。项目2，由 Marcia McDuffie 博士领导的团队将根据上一资助期间确定的染色体位点，确定 SAMP 小鼠中与回肠炎易感性相关的易感基因。项目 3 由 Steven Cohn 博士领导，将研究潘氏细胞及其防御素在引发回肠炎中的作用。项目 4 由 Klaus Ley 博士领导，将研究 SAMP 小鼠中淋巴细胞归巢和运输的机制，特别关注 L-选择素和 PSGL-1。项目 5 是由 Theresa Pizarro 博士领导的一个新项目，将研究上皮先天免疫反应在 SAMP 小鼠回肠炎的引发和持续中的作用。该计划得到协调该计划的行政核心和动物 Core，集中生产和饲养 SAMP 小鼠和其他同类系。该计划项目的长期目标是了解实验性 CD 的关键致病机制，以帮助开发治疗至少一部分患有这种破坏性疾病的患者的治疗方法。