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

Comments

Full author list omitted for brevity. For the full list of authors, see article.

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Science translational medicine

PubMed ID

34516831

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