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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.

摘要白癜风是一种以皮肤上积累白色斑块为特征的疾病，免疫介导的黑素细胞破坏。窄带NBUVB光疗法，金标准治疗对于白癜风，诱导黑素细胞从毛囊迁移到表皮重新着色。手术这些方法还可以替代被免疫系统耗尽的表皮黑素细胞储库，达到与光疗法类似的再色素沉着结果。虽然这些疗法部分成功，所观察到的再色素沉着很少是完全的--受影响的白癜风皮肤区域经常在再色素沉着之间保留，色素沉着区。目前尚不清楚这种现象是否是因为免疫系统清除了黑素细胞在前沿阻止全面反应，白癜风角质形成细胞迁移抑制黑素细胞或黑素细胞不能完全迁移以填充迁移的差距。我们最近开发了非侵入性的方法来观察表皮内黑色素细胞的横向迁移在白癜风重新色素沉着，让我们第一次看到动态表皮黑素细胞生态位。在在这项应用中，我们试图使用这种新技术来可视化白癜风重新色素沉着的动态，并确定再色素沉着的程度是否受到限制黑素细胞的局部因素的限制迁移或通过免疫系统去除黑素细胞。为了更好地了解细胞球员，调节重新色素沉着的过程中，我们将进行单细胞RNA测序正常皮肤、对光疗法有部分反应的皮肤和对光疗法无反应的皮肤目的：1）确定迁移黑素细胞的分子特征; 2）确定是否存在独特的与正常皮肤相比，白癜风皮肤中的角质形成细胞群可以抑制黑素细胞迁移; 3）鉴定诱导局部破坏的推定免疫信号和免疫效应物，黑素细胞完成这些研究对于制定新的战略以改善现有的白癜风的治疗