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

Zhaohuai Li; Mei Wang; Jia Tan; Lei Zhu; Peng Zeng; Xiaozhen Chen; Lihui Xie; Runping Duan; Binyao Chen; Tianyu Tao; Rong Wang; Xianggui Wang; Wenru Su

doi:10.1016/j.xcrm.2022.100699

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.

Authors

Zhaohuai Li¹, Mei Wang², Jia Tan³, Lei Zhu¹, Peng Zeng², Xiaozhen Chen⁴, Lihui Xie¹, Runping Duan¹, Binyao Chen¹, Tianyu Tao¹, Rong Wang¹, Xianggui Wang⁵, Wenru Su⁶

Affiliations

¹ State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
² Department of Ophthalmology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
³ Eye Center of Xiangya Hospital, Hunan Key Laboratory of Ophthalmology, Xiangya Hospital, Central South University, Changsha 410078, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410078, China.
⁴ Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha 410008, China.
⁵ Eye Center of Xiangya Hospital, Hunan Key Laboratory of Ophthalmology, Xiangya Hospital, Central South University, Changsha 410078, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410078, China. Electronic address: wangxg@csu.edu.cn.
⁶ State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China. Electronic address: suwr3@mail.sysu.edu.cn.

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