Leukocyte Immunoglobulin-like Receptors in Cutaneous Host Defense

描述(由申请人提供)： 这份提案描述了一项为期5年的皮肤病学术生涯发展培训计划。这位首席研究员已经完成了她在加州大学洛杉矶分校的皮肤病住院医师结构化培训的90%以上，目前正在通过一项致力于促进学术医学职业生涯的计划来扩展她的科学技能，该计划将皮肤病住院医师培训与两年受保护的博士后研究奖学金相结合。这项计划将促进对细胞免疫学的掌握，如应用于皮肤科传染病麻风。罗伯特·莫德林博士将指导首席研究员的科学发展，他是麻风病领域公认的领导者，目前他的实验室正在进行的研究涉及宿主防御机制和皮肤的先天免疫机制，这两项机制都与这一提议相关。这位首席研究员的长期职业目标是成为皮肤科学术领域的独立研究员，并拥有自己的实验室。研究将集中在利用麻风病，一种取决于宿主免疫反应的临床结果谱疾病，来研究一种新的受体家族--白细胞免疫球蛋白样受体(LILR)在免疫失调中的作用。莫德林博士实验室最近的工作通过基因图谱研究发现，与自愈型结核病相比，进行性麻风患者中LILR家族成员的表达增加。拟议的实验将需要进一步分析LILR在麻风中的表达，以及调查LILR家族成员的功能。其具体目的包括：1)确定表达特定LILR家族成员的麻风皮损中的细胞类型(S)，2)评价LILR在天然免疫调节中的作用，3)研究LILR激活是否影响获得性免疫反应。多种药物疗法仍然没有根除麻风病，全世界大约有100万人受到影响，仍然给发展中国家带来巨大的健康和经济负担。从LILR的研究中获得的见解，在麻风病中发现的水平增加，将有助于扩大我们对先天性和获得性免疫系统的免疫调节的理解，并可能导致开发治疗这种和其他传染病的免疫疗法。

DESCRIPTION (provided by applicant): This proposal describes a 5 year training program for the development of an academic career in Dermatology. The principal investigator has completed over 90% of her structured residency training in Dermatology at UCLA, and is currently expanding her scientific skills through a program committed to promoting careers in academic medicine by integrating dermatology residency training with a two-year protected postdoctoral research fellowship. This program will promote the command of cellular immunology, as applied to the dermatologic infectious disease, leprosy. Dr. Robert Modlin will mentor the principal investigator's scientific development and is a recognized leader in the field of leprosy, with current ongoing studies in his laboratory involving the mechanisms of host defense and innate immunity in skin, both of which are relevant to this proposal. The principal investigator's long-term career goal is to be an independent investigator in academic dermatology with her own laboratory. Research will focus on using leprosy, a disease with a spectrum of clinical outcomes depending on the host immune response, to study the role of a novel family of receptors, the leukocyte immunoglobulin-like receptors (LILRs) in immune dysregulation. Recent work in Dr. Modlin's laboratory identified an increased expression of LILR family members in the progressive lepromatous form of leprosy compared to the selfhealing tuberculoid form by gene profiling studies. The proposed experiments will entail further analysis of the expression of LILRs in leprosy as well as investigation of the function of the LILR family members. The specific aims include: 1) identifying the cell type(s) in leprosy lesions that express particular LILR family members, 2) evaluating the roles of LILRs in regulation of innate immunity, and 3) investigating whether LILR activation affects adaptive immune responses. Multidrug therapy still has not eradicated leprosy, affecting approximately one million people worldwide still poses a significant health and economic burden on developing countries. The insights gained from the study of LILRs, found at increased levels in lepromatous leprosy, will help broaden our understanding of immunoregulation of the innate and adaptive immune systems and may lead to the development of immunotherapies to treat this and other infectious diseases.