Dendritic cells in psoriasis and effects of efalizumab

牛皮癣中的树突状细胞和依法珠单抗的作用

• 批准号: 7034155
• 负责人: MICHELLE A LOWES
• 金额: $ 13.54万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7034155
• 关键词: CD antigens; T lymphocyte; biomarker; biopsy; blood; cell differentiation; cell population study; clinical research; dendritic cells; flow cytometry; genetic screening; genotype; human subject; immunocytochemistry; immunofluorescence technique; immunogenetics; immunomodulators; immunopharmacology; leukocyte activation /transformation; leukocyte adhesion molecules; microarray technology; monoclonal antibody; pathologic process; patient oriented research; psoriasis; skin

DESCRIPTION (provided by applicant): CANDIDATE: I am a dermatologist (MD PhD) and my broad career goal is to be an independent physician scientist in human translational skin research, particularly in the area of psoriasis. I am proposing to become a multi-disciplinary patient-oriented researcher, with an excellent grasp of a number of technologies, which will allow me to investigate therapeutic, mechanistic and pathologic questions appropriately and deeply. ENVIRONMENT: Rockefeller University is a world-renowned institution with a rich history of bench-bedside research. It provides an ideal environment to carry out this type of clinical research with a dedicated GCRC-funded research hospital, outstanding laboratories, excellent core facilities and equipment, an innovative Clinical Scholars Program for translational research trainees, and several inspiring lecture and seminar programs. There is no fee-for-service medicine at Rockefeller University, so I can dedicate 100% of my time to this career development plan. RESEARCH PROJECT: Psoriasis offers an excellent model of type 1 autoimmunity, and there is no ideal animal model of psoriasis to study. In the context of a clinical trial with efalizumab (anti-CD11a) for psoriasis, we identified a new type of cutaneous dendritic cell (DC) (CD11c+, HLA-DR+, CD86+, CD40+), which constitutes the most abundant type of leukocyte in psoriasis lesions. It also expresses TNF and iNOS, so these cells may be the human equivalent of recently described murine TNF- and indicible nitric oxide synthase (iNOS)-producing (TIP)-DCs. I plan to begin basic characterization of complex DC subsets that exist in blood and skin of humans, using efalizumab as a tool to modulate psoriasis disease activity, so that the contribution of different DC subsets to disease pathogenesis can be better refined. Furthermore, I will determine the extent to which efalizumab has direct effects on growth, differentiation and activation of DCs versus indirect effects through T cell modulation.

描述（由申请人提供）： 候选人：我是一名皮肤科医生（医学博士），我的广泛职业目标是成为人类转化皮肤研究的独立医师科学家，特别是在牛皮癣领域。我打算成为一名以患者为中心的多学科研究人员，精通多种技术，这将使我能够适当而深入地研究治疗、机制和病理问题。环境：洛克菲勒大学是一所世界知名的机构，拥有丰富的临床研究历史。它为开展此类临床研究提供了理想的环境，拥有 GCRC 资助的专门研究医院、出色的实验室、卓越的核心设施和设备、针对转化研究实习生的创新临床学者计划以及多个鼓舞人心的讲座和研讨会项目。洛克菲勒大学没有收费医疗，所以我可以把100%的时间奉献给这个职业发展计划。 研究项目：银屑病提供了一种优秀的 1 型自身免疫模型，但目前还没有理想的银屑病动物模型可供研究。在使用 efalizumab（抗 CD11a）治疗银屑病的临床试验中，我们发现了一种新型皮肤树突状细胞 (DC)（CD11c+、HLA-DR+、CD86+、CD40+），它构成了银屑病皮损中最丰富的白细胞类型。它还表达 TNF 和 iNOS，因此这些细胞可能是最近描述的鼠类 TNF 和可指示一氧化氮合酶 (iNOS) 产生 (TIP)-DC 的人类等同物。我计划开始对人类血液和皮肤中存在的复杂 DC 亚群进行基本表征，使用 efalizumab 作为调节银屑病疾病活动的工具，以便更好地细化不同 DC 亚群对疾病发病机制的贡献。此外，我将确定 efalizumab 对 DC 生长、分化和激活的直接影响与通过 T 细胞调节产生的间接影响的程度。