Research Paper Volume 16, Issue 9 pp 8217—8245
Single-cell BCR and transcriptome analysis reveals peripheral immune signatures in patients with thyroid-associated ophthalmopathy
- 1 Department of Ophthalmology, Peoples’ Hospital of Ningxia Hui Autonomous Region, The Third Affiliated Clinical College of Ningxia Medical University, Yinchuan, Ningxia, P.R. China
- 2 Medical Science Research Institution of Ningxia Hui Autonomous Region, Medical Sci-Tech Research Center of Ningxia Medical University, Yinchuan, Ningxia, P.R. China
- 3 Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, P.R. China
- 4 Department of Ophthalmology, Guro Hospital, Korea University College of Medicine, Guro-gu, Seoul 152–703, South Korea
Received: November 17, 2023 Accepted: April 9, 2024 Published: May 9, 2024
https://doi.org/10.18632/aging.205814How to Cite
Copyright: © 2024 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Thyroid-associated ophthalmopathy (TAO) is the most prevalent orbital disease in adults caused by an autoimmune disorder, which can lead to disfigurement and vision impairment. Developing effective treatments for this condition presents challenges due to our limited understanding of its underlying immune aberrations. In this study, we profiled the immune components in the peripheral blood of patients with TAO as well as healthy individuals, utilizing single-cell RNA sequencing and B-cell receptor repertoires (BCR) analysis. We observed a significant reduction in the proportions of regulatory B cells (Bregs) and type 2 conventional dendritic cells (DCs) in patients with TAO during the active phase. Conversely, there was a significant increase in the proportion of type 1 DCs. Further analysis of cell differentiation trajectory revealed potential impairment in the transition of B cells towards Breg phenotype during the active phase of TAO. Besides, the activation process of TAO appeared to involve inflammation and immune dysfunction, as indicated by the dynamic changes in the activities of key regulators. The abnormalities in the peripheral immune system, such as the reduced capacity of Bregs to suppress inflammation, were primarily driven by the enhanced interaction among Breg, DCs, and monocytes (i.e., CD22-PTPRC and BTLA-TNFRSF14). Collectively, our findings offer a comprehensive insight into the molecular regulation and cellular reconfiguration during the active phase of TAO at the single-cell level, in order to explore the pathogenesis of TAO and provide new ideas for the future treatment of TAO.
Abbreviations
TAO: thyroid-associated ophthalmopathy; BCR: B-cell receptor repertoires; Bregs: regulatory B cells; DCs: dendritic cells; GD: Graves’ disease; EOM: extraocular muscles; OFs: orbital fibroblasts; TSIs: thyroid-stimulating immunoglobulins; APC: antigen presenting cells; IFN-γ: interferon-γ; TNF-α: tumor necrosis factor-α; IL-1β: interleukin-1β; scRNA-seq: single-cell RNA sequencing; scBCR-seq: single-cell BCR sequencing; PBMCs: peripheral blood mononuclear cells; NCs: normal controls; cDC2s: type 2 conventional dendritic cells; cDC1s: type 1 conventional dendritic cells; CMOs: classical monocytes; NMOs: non-classical monocytes; IMOs: intermediate monocytes; TLR: toll-like receptor; DEGs: different expression genes; BTLA: B and T lymphocyte attenuator.