Document Type

Article

Publication Date

3-1-2021

Publication Title

Cell Mol Immunol

Keywords

JGM, CD4-Positive T-Lymphocytes, Chemotaxis, Graves Ophthalmopathy, Humans, Inflammation, RNA-Seq, Receptors, Antigen, T-Cell, Single-Cell Analysis, T-Lymphocytes, Cytotoxic

JAX Source

Cell Mol Immunol 2021 Mar; 18(3):735-745

Volume

18

Issue

3

First Page

735

Last Page

745

ISSN

2042-0226

PMID

33514849

DOI

https://doi.org/10.1038/s41423-020-00615-2

Abstract

Graves' orbitopathy (GO), the most severe manifestation of Graves' hyperthyroidism (GH), is an autoimmune-mediated inflammatory disorder, and treatments often exhibit a low efficacy. CD4+ T cells have been reported to play vital roles in GO progression. To explore the pathogenic CD4+ T cell types that drive GO progression, we applied single-cell RNA sequencing (scRNA-Seq), T cell receptor sequencing (TCR-Seq), flow cytometry, immunofluorescence and mixed lymphocyte reaction (MLR) assays to evaluate CD4+ T cells from GO and GH patients. scRNA-Seq revealed the novel GO-specific cell type CD4+ cytotoxic T lymphocytes (CTLs), which are characterized by chemotactic and inflammatory features. The clonal expansion of this CD4+ CTL population, as demonstrated by TCR-Seq, along with their strong cytotoxic response to autoantigens, localization in orbital sites, and potential relationship with disease relapse provide strong evidence for the pathogenic roles of GZMB and IFN-γ-secreting CD4+ CTLs in GO. Therefore, cytotoxic pathways may become potential therapeutic targets for GO.

Comments

This article is licensed under a Creative Commons Attribution 4.0 International License.

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