Single-cell RNA sequencing depicts the local cell landscape in thyroid-associated ophthalmopathy

Cell Rep Med. 2022 Aug 16;3(8):100699. doi: 10.1016/j.xcrm.2022.100699. Epub 2022 Jul 26.

Abstract

There is a specific reactivity and characteristic remodeling of the periocular tissue in thyroid-associated ophthalmopathy (TAO). However, local cell changes responsible for these pathological processes have not been sufficiently identified. Here, single-cell RNA sequencing is performed to characterize the transcriptional changes of cellular components in the orbital connective tissue in individuals with TAO. Our study shows that lipofibroblasts with RASD1 expression are highly involved in inflammation and adipogenesis during TAO. ACKR1+ endothelial cells and adipose tissue macrophages may engage in TAO pathogenesis. We find CD8+CD57+ cytotoxic T lymphocytes with the terminal differentiation phenotype to be another source of interferon-γ, a molecule actively engaging in TAO pathogenesis. Cell-cell communication analysis reveals increased activity of CXCL8/ACKR1 and TNFSF4/TNFRSF4 interactions in TAO. This study provides a comprehensive local cell landscape of TAO and may be valuable for future therapy investigation.

Keywords: autoimmune disease; orbital fibroblast; single-cell RNA sequencing; thyroid-associated ophthalmopathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipogenesis / genetics
  • Endothelial Cells / metabolism
  • Graves Ophthalmopathy* / genetics
  • Humans
  • OX40 Ligand / genetics
  • Orbit / metabolism
  • Sequence Analysis, RNA
  • ras Proteins / genetics

Substances

  • OX40 Ligand
  • RASD1 protein, human
  • TNFSF4 protein, human
  • ras Proteins