Abstract
There is a specific reactivity and characteristic remodeling of the periocular tissue in thyroid-associated ophthalmopathy (TAO). However, the cellular components responsible for these changes have not been sufficiently identified. Here, single-cell RNA sequencing was performed to characterize the transcriptional properties of cellular components in the orbital connective tissue in TAO patients. RASD1 expression in orbital fibroblasts defines lipofibroblastic phenotypes. These celltypes specifically expresses adipogenic differentiation associated genes. ACKR1+ Endothelial cells and adipose tissue macrophages are also involved in the disease process. Our study then highlights CD8+CD57+KLRG1+ cytotoxic T lymphoid cells with terminal differentiation phenotype as sources of sustained interferon-γ secretion. Moreover, cell–cell communication analysis revealed evidence of increased activity of the ACKR1/CXCL8 and TNFSF4/TNFRSF4 systems in TAO, which is consistent with stronger inflammatory cell infiltrating and fibrosis response. These cells in the orbital connective tissue constitute an orbital fibroblast-based cell-cell interaction network that regulates the pathogenesis of TAO.
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