UMass Chan Medical School Faculty Publications
Title
scRNA-seq of human vitiligo reveals complex networks of subclinical immune activation and a role for CCR5 in Treg function
UMMS Affiliation
Program in Bioinformatics and Integrative Biology; Department of Dermatology; Graduate School of Biomedical Sciences; Garber Lab
Publication Date
2021-09-08
Document Type
Article
Disciplines
Dermatology | Hemic and Immune Systems | Immune System Diseases | Immunity | Immunopathology | Skin and Connective Tissue Diseases
Abstract
Vitiligo is an autoimmune skin disease characterized by the targeted destruction of melanocytes by T cells. Cytokine signaling between keratinocytes and T cells results in CD8+ T cell infiltration of vitiligo lesions, but the full scope of signals required to coordinate autoimmune responses is not completely understood. We performed single-cell RNA sequencing on affected and unaffected skin from patients with vitiligo, as well as healthy controls, to define the role of each cell type in coordinating autoimmunity during disease progression. We confirmed that type 1 cytokine signaling occupied a central role in disease, but we also found that this pathway was used by regulatory T cells (Tregs) to restrain disease progression in nonlesional skin. We determined that CCL5-CCR5 signaling served as a chemokine circuit between effector CD8+ T cells and Tregs, and mechanistic studies in a mouse model of vitiligo revealed that CCR5 expression on Tregs was required to suppress disease in vivo but not in vitro. CCR5 was not required for Treg recruitment to skin but appeared to facilitate Treg function by properly positioning these cells within the skin. Our data provide critical insights into the pathogenesis of vitiligo and uncover potential opportunities for therapeutic interventions.
Keywords
UMCCTS funding, vitiligo
DOI of Published Version
10.1126/scitranslmed.abd8995
Source
Gellatly KJ, Strassner JP, Essien K, Refat MA, Murphy RL, Coffin-Schmitt A, Pandya AG, Tovar-Garza A, Frisoli ML, Fan X, Ding X, Kim EE, Abbas Z, McDonel P, Garber M, Harris JE. scRNA-seq of human vitiligo reveals complex networks of subclinical immune activation and a role for CCR5 in Treg function. Sci Transl Med. 2021 Sep 8;13(610):eabd8995. doi: 10.1126/scitranslmed.abd8995. Epub 2021 Sep 8. PMID: 34516831; PMCID: PMC8686160. Link to article on publisher's site
Related Resources
Journal/Book/Conference Title
Science translational medicine
PubMed ID
34516831
Repository Citation
Gellatly K, Strassner JP, Essien KI, Ahmed Refat M, Murphy RL, Coffin-Schmitt A, Frisoli ML, Fan X, Kim EE, Abbas Z, McDonel P, Garber M, Harris JE. (2021). scRNA-seq of human vitiligo reveals complex networks of subclinical immune activation and a role for CCR5 in Treg function. UMass Chan Medical School Faculty Publications. https://doi.org/10.1126/scitranslmed.abd8995. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/2180
Comments
Full author list omitted for brevity. For the full list of authors, see article.