Intestinal Dendritic Cell Modulation of Regulatory T Cell Function in IBD

IBD 中调节性 T 细胞功能的肠道树突状细胞调节

• 批准号: 7513622
• 负责人: James Daniel Lord
• 金额: $ 14.75万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-25 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7513622
• 关键词: Autoimmune Process; Biological Assay; Blocking Antibodies; CD4 Positive T Lymphocytes; Cell Differentiation process; Cell physiology; Cell surface; Cells; Cellular Immunology; Chronic; Clinical; Coculture Techniques; Communities; Condition; Data; Dendritic Cells; Development Plans; Doctor of Medicine; Doctor of Philosophy; Educational Curriculum; Exercise; Fostering; Gastroenterology; Human; Human Resources; Immune system; Immunology; In Vitro; Inflammation; Inflammatory; Inflammatory Bowel Diseases; Inflammatory disease of the intestine; Intestines; Ligands; Link; Mediating; Medical center; Mentorship; Molecular; Pacific Northwest; Patients; Pattern; Personal Satisfaction; Physicians; Public Health; Range; Recombinant Antibody; Recruitment Activity; Reporting; Research; Research Institute; Research Personnel; Resected; Resistance; Signal Transduction; Sorting - Cell Movement; Study Subject; Surface; T-Cell Proliferation; T-Lymphocyte; Testing; Today; Universities; Virginia; Washington; career; cytokine; design; forging; in vivo; prevent; programs; receptor; research facility; research study; symposium; transcription factor

DESCRIPTION (provided by applicant): Project Summary: Dr. James Lord, M.D., Ph.D., is a motivated senior gastroenterology fellow with a strong background in basic immunology research. His immediate career plans involve understanding how regulatory T cells (Tregs) fail to prevent inflammation in inflammatory bowel disease. He proposes to study dendritic cells (DC) in the surgically resected bowels of patients with IBD, to determine if and how certain subtypes of DC prevent Tregs from inhibiting other T cells. He plans to identify the surface receptors and soluble cytokines produced by these DC, and determine if these may impair Treg function. He also will determine if DC indirectly impair Treg function by altering the differentiation of other T cells to become less responsive to Treg-mediated inhibition. This research will be performed under the mentorship of Steven Ziegler, a well-established Treg biologist. The Ziegler lab is well equipped for molecular and cellular immunology research, and exists within the Benaroya Research Institute (BRI). The BRI is an academic research facility dedicated to the study of autoimmune and chronic inflammatory conditions, and as such contains many material and human resources vital to the study of human immunology. The BRI is itself affiliated with the University of Washington, which represents a large, prestigious and vibrant reseach [sic] community. The BRI is also affiliated with, and recruits study subjects from, the Virginia Mason Medical Center, which is one of the busiest tertiary referral centers for IBD in the Pacific Northwest. Dr. Lord's long-term career plans involve building upon his dual backgrounds in clinical gastroenterology and basic immunology to forge a link between the large clinical gastroenterology community and the strong basic immunology research community currently present in Seattle. His career development plan outlines a curriculum of research, didactic coursework, and local and national conference attendance, designed to foster his maturation into a successful translational researcher. Relevance to Public Health: Despite significant advances in our understanding of the immune system, IBD remains incurable, poorly understood, and both challenging and expensive to treat. If the proposed experiments reveal a fundamental mechanism by which IBD occurs, they may not only reveal new potential treatment strategies for tomorrow, but also allow physicians to better target the treatments they have today.

描述（由申请人提供）： 项目摘要：詹姆斯·洛德（James Lord）博士，博士学位，是一个有动力的高级胃肠病学研究员，具有基本免疫学研究的良好背景。他的直接职业计划涉及了解调节性T细胞（TREG）如何无法防止炎症性肠病中的炎症。他建议在手术切除的IBD患者的肠道中研究树突状细胞（DC），以确定DC的某些亚型是否以及如何阻止Treg抑制其他T细胞。他计划鉴定这些DC产生的表面受体和可溶性细胞因子，并确定这些表面受体和可溶性细胞因子是否会损害Treg功能。他还将通过改变其他T细胞的分化以降低对Treg介导的抑制作用的反应较低，从而确定DC是否间接损害了Treg功能。这项研究将在史蒂文·齐格勒（Steven Ziegler）的指导下进行，这是一位良好的Treg生物学家。 Ziegler Lab具有很好的分子和细胞免疫学研究，并且存在于Benaroya研究所（BRI）内。 BRI是一种专门研究自身免疫性和慢性炎症状况的学术研究机构，因此包含许多对人类免疫学研究至关重要的物质和人力资源。 BRI本身隶属于华盛顿大学，该大学代表了一个庞大，享有声望和充满活力的研究社区。 BRI还隶属于弗吉尼亚梅森医疗中心的新兵研究主题，该中心是西北太平洋地区最繁忙的IBD的最繁忙的第三次转诊中心之一。 Lord博士的长期职业计划涉及基于他在临床胃肠病学和基本免疫学方面的双重背景，以在大型临床胃肠病学界与目前在西雅图目前存在的强大基本免疫学研究界建立联系。他的职业发展计划概述了研究，教学课程以及本地和全国会议的课程，旨在促进他的成熟为成功的转化研究员。 与公共卫生有关：尽管我们对免疫系统的理解取得了重大进展，但IBD仍然无法治愈，理解不足，既有挑战又昂贵。如果提出的实验揭示了IBD发生的基本机制，它们不仅可能揭示明天的新潜在治疗策略，而且还允许医生更好地针对他们今天的治疗方法。