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Identifying the Molecular Characteristics of Migrating Melanocytes in Vitiligo Skin

鉴定白癜风皮肤中迁移的黑素细胞的分子特征

基本信息

批准号：
9762842
负责人：
Anand K Ganesan
金额：
$ 20.39万
依托单位：
UNIVERSITY OF CALIFORNIA-IRVINE
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-15 至 2021-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9762842
关键词：
Affect Area Autoimmune Process Bilateral Cell Transplantation Cell Transplants Cells Characteristics Clinical Disease Epidermis Gold Hair follicle structure Harvest Human Immune Immune response Immune signaling Immune system In complete remission Lesion Measures Mediating Methods Microscopy Molecular Operative Surgical Procedures Organ Transplantation Patients Phototherapy Pigmentation physiologic function Pigments Population Procedures Process Publishing Side Signal Transduction Site Skin Skin graft Technology Testing Time Transplantation Tumor-infiltrating immune cells Ultraviolet Therapy Vitiligo Work base comparative design imaging modality improved in vivo innovation keratinocyte melanocyte microscopic imaging migration multiphoton microscopy new technology non-invasive imaging novel prevent reconstitution recruit response single-cell RNA sequencing standard care transcriptome sequencing transcriptomics ultraviolet ultraviolet irradiation

项目摘要

Abstract Vitiligo is a disease characterized by the accumulation of white patches on the skin, the direct result of immune-mediated melanocyte destruction. Narrow band NBUVB light therapy, the gold standard treatment for vitiligo, induces melanocytes to migrate from the hair follicle to re-pigment the epidermis. Surgical approaches can also replace the epidermal melanocyte reservoir depleted by the immune system, achieving similar re-pigmentation results as light therapy. While these therapies are partially successful, the observed re-pigmentation is rarely complete- areas of affected vitiligo skin often remain between re- pigmented areas. It is currently unclear whether this phenomenon is because the immune system removes melanocytes at the leading edge preventing a full response, vitiligo keratinocytes inhibit the migration of melanocytes, or melanocytes are not able to migrate completely to fill the gap migrate. We have recently developed non-invasive methods to visualize the migration of melanocytes laterally within the epidermis during vitiligo re-pigmentation, giving us the first glimpse of the dynamic epidermal melanocyte niche. In this application, we seek to use this novel technology to visualize the dynamics of vitiligo re-pigmentation and determine whether the extent of re-pigmentation is limited by local factors that limit melanocyte migration or by the immune system, which removes melanocytes. To gain a better sense of the cellular players that regulate the re-pigmentation process, we will perform single cell RNA sequencing on normal skin, skin that has partially responded to light therapy, and skin that did not respond to light therapy in order to: 1) define the molecular characteristics of migrating melanocytes; 2) identify whether there are unique populations of keratinocytes in vitiligo skin as compared to normal skin that could inhibit melanocyte migration; 3) identify putative immune signals and immune effectors that induce local destruction of melanocytes. Completion of these studies will be critical in developing new strategies to improve existing vitiligo therapies.

摘要