Intestinal Dendritic Cell Modulation of Regulatory T Cell Function in IBD

描述（由申请人提供）： 项目摘要：James Lord 博士是一位积极主动的胃肠病学高级研究员，具有深厚的基础免疫学研究背景。他近期的职业计划包括了解调节性 T 细胞 (Treg) 为何无法预防炎症性肠病中的炎症。他提议研究 IBD 患者手术切除肠道中的树突状细胞 (DC)，以确定 DC 的某些亚型是否以及如何阻止 Tregs 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，并确定它们是否可能损害 Treg 功能。他还将确定 DC 是否通过改变其他 T 细胞的分化以降低对 Treg 介导的抑制的反应来间接损害 Treg 功能。这项研究将在著名 Treg 生物学家 Steven Ziegler 的指导下进行。齐格勒实验室位于贝纳罗亚研究所 (BRI) 内，设备齐全，适合分子和细胞免疫学研究。 BRI 是一个致力于研究自身免疫和慢性炎症性疾病的学术研究机构，因此拥有许多对人类免疫学研究至关重要的物质和人力资源。 “一带一路”本身隶属于华盛顿大学，该大学代表着一个大型、享有盛誉且充满活力的研究团体。 BRI 还隶属于弗吉尼亚梅森医疗中心，并从该中心招募研究对象，该中心是太平洋西北地区最繁忙的 IBD 三级转诊中心之一。 Lord 博士的长期职业计划涉及利用他在临床胃肠病学和基础免疫学方面的双重背景，在西雅图目前大型临床胃肠病学界和强大的基础免疫学研究界之间建立联系。他的职业发展计划概述了研究课程、教学课程以及参加地方和国家会议，旨在促进他成熟为一名成功的转化研究员。 与公共卫生的相关性：尽管我们对免疫系统的了解取得了重大进展，但 IBD 仍然无法治愈、了解甚少，而且治疗起来既具有挑战性又昂贵。如果所提出的实验揭示了IBD发生的基本机制，它们不仅可能揭示未来新的潜在治疗策略，而且还可以让医生更好地针对他们今天的治疗。

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.