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

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. [Display omitted] •A local transcriptional landscape of orbital connective tissue in TAO is developed•RASD1-expressing lipofibroblasts are highly involved in adipogenesis and inflammation•ACKR1+ endothelial cells contribute to inflammatory cell infiltration in TAO•Adipose tissue macrophages engage in lipid metabolism and inflammatory response in TAO Thyroid-associated ophthalmopathy, characterized by orbital tissue expansion, remodeling, and fibrosis, commonly occurs in individuals with Graves’ diseases and will threaten eyesight in its most severe form. Li et al. perform single-cell RNA sequencing in orbital tissues of individuals with TAO to identify transcriptional changes, which may serve therapeutic optimization.