Leukocyte Immunoglobulin-like Receptors in Cutaneous Host Defense

描述（由申请人提供）： 该提案描述了一个为期5年的培训计划，以发展皮肤科的学术生涯。主要研究者已经完成了她在加州大学洛杉矶分校皮肤科的结构化住院医师培训的90%以上，目前正在通过一项致力于通过将皮肤科住院医师培训与为期两年的受保护博士后研究奖学金相结合来促进学术医学事业的计划来扩展她的科学技能。该计划将促进细胞免疫学的命令，适用于皮肤传染病，麻风病。Robert Modlin博士将指导主要研究者的科学发展，他是麻风病领域公认的领导者，目前正在他的实验室进行的研究涉及宿主防御和皮肤先天免疫的机制，两者都与本提案有关。首席研究员的长期职业目标是成为一名独立的学术皮肤病学研究员，拥有自己的实验室。研究将侧重于使用麻风病，一种具有取决于宿主免疫反应的一系列临床结果的疾病，来研究一种新的受体家族，即白细胞免疫球蛋白样受体（LILR）在免疫失调中的作用。Modlin博士实验室最近的工作通过基因分析研究发现，与自愈性结核样形式相比，LILR家族成员在进行性麻风瘤型中的表达增加。拟议的实验将需要进一步分析LILR在麻风病中的表达，以及LILR家族成员的功能调查。具体目标包括：1）鉴定麻风病病灶中表达特定LILR家族成员的细胞类型，2）评估LILR在先天免疫调节中的作用，和3）研究LILR活化是否影响适应性免疫应答。 多种药物疗法仍然没有根除麻风病，全世界大约有100万人感染麻风病，仍然对发展中国家造成重大的健康和经济负担。从LILR研究中获得的见解，在麻风瘤型麻风中发现的水平增加，将有助于扩大我们对先天和适应性免疫系统免疫调节的理解，并可能导致免疫疗法的发展来治疗这种疾病和其他传染病。

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.