Leukocyte Immunoglobulin-like Receptors in Cutaneous Host Defense

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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.