Leukocyte Immunoglobulin-like Receptors in Cutaneous Host Defense

皮肤宿主防御中的白细胞免疫球蛋白样受体

• 批准号: 7579773
• 负责人: Delphine J Lee
• 金额: $ 11.34万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-05 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7579773
• 关键词: Affect; Allogenic; Antigen Presentation; Antigen-Presenting Cells; Autoantigens; Bacteria; Blood; CD14 gene; CD80 gene; Cell Maturation; Cell surface; Cells; Cellular Immunology; Clinical; Commit; Communicable Diseases; Confocal Microscopy; Cutaneous; Data; Dendritic Cells; Dermatologic; Dermatology; Developed Countries; Developing Countries; Development; Disease; Doctor of Medicine; Doctor of Philosophy; Economic Burden; Family; Family member; Fellowship; Figs - dietary; Frequencies; Gene Expression Microarray Analysis; Genes; Goals; Histocompatibility Antigens Class II; Host Defense; Host Defense Mechanism; ITGAX gene; Immune; Immune Tolerance; Immune response; Immune system; Immunity; Immunoglobulins; Immunohistochemistry; Immunotherapy; Infection; Interleukin-10; Interleukin-12; Investigation; Label; Laboratories; Lead; Lepromatous Leprosy; Leprosy; Lesion; Leukocytes; Ligands; Major Histocompatibility Complex; Mediating; Medicine; Memory; Mentors; Messenger RNA; Modeling; Monoclonal Antibodies; Mycobacterium leprae; Natural Immunity; Outcome; Patients; Pattern; Population; Principal Investigator; Production; Program Development; Protein Isoforms; Prunella vulgaris; Receptor Activation; Regulation; Research; Research Personnel; Residencies; Role; Skin; Structure; T memory cell; T-Cell Activation; T-Lymphocyte; Testing; Toll-like receptors; Training; Training Programs; Up-Regulation; Work; antimicrobial; career; cell mediated immune response; cell type; comparative; crosslink; cytokine; health economics; immunoregulation; insight; killings; macrophage; member; monocyte; novel; pathogen; peripheral blood; programs; receptor; receptor expression; research study; response; skills; skin lesion

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 self- healing 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.

这项建议描述了一项为期5年的培训计划，目的是为了在 皮肤科。首席调查员已经完成了90%以上的结构化住院医师培训 皮肤科，目前正在通过一个致力于 将皮肤科住院医师培训与两年制相结合促进学术医学职业发展 受保护的博士后研究奖学金。这个项目将促进对细胞免疫学的指挥， 适用于皮肤科传染病、麻风病。罗伯特·莫德林博士将指导校长 研究人员的科学发展，是麻风病领域公认的领导者，目前正在进行 他在实验室中的研究涉及皮肤的寄主防御和天然免疫机制，这两者都 都与这项提议有关。首席调查员的长期职业目标是成为一名独立的 她是皮肤科学术研究人员，拥有自己的实验室。 研究将集中在使用麻风病，一种疾病的临床结果取决于 宿主免疫反应，研究一种新的受体家族--白细胞免疫球蛋白样蛋白的作用 免疫失调中的受体(LILRs)莫德林博士实验室最近的研究发现， LILR家族成员在进展型麻风中的表达与自身对照 通过基因图谱研究治愈类结核。拟议的实验将需要进一步分析 LILR在麻风中的表达及其家族成员功能的研究这个 具体目标包括：1)在表达特定ILR家族的麻风皮损中鉴定细胞类型(S) 成员，2)评估LILR在调节先天免疫中的作用，以及3)调查LILR是否 激活会影响适应性免疫反应。 多种药物治疗仍未根除麻风，全球约有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。从以下方面获得的见解： 对LILR的研究，发现在麻风病中水平升高，将有助于拓宽我们对 先天免疫系统和获得性免疫系统的免疫调节，并可能导致 治疗这种疾病和其他传染病的免疫疗法。