Defective Regulatory B Cells Are Associated With Thyroid-Associated Ophthalmopathy

Guo Chen; Yungang Ding; Qian Li; Yanbing Li; Xiaofeng Wen; Xian Ji; Shaowei Bi; Jingqiao Chen; Jianan Xu; Rongxin Chen; Huijing Ye; Lai Wei; Huasheng Yang

doi:10.1210/jc.2018-01812

Defective Regulatory B Cells Are Associated With Thyroid-Associated Ophthalmopathy

J Clin Endocrinol Metab. 2019 Sep 1;104(9):4067-4077. doi: 10.1210/jc.2018-01812.

Authors

Guo Chen¹, Yungang Ding¹, Qian Li^{1

2}, Yanbing Li³, Xiaofeng Wen¹, Xian Ji¹, Shaowei Bi, Jingqiao Chen¹, Jianan Xu¹, Rongxin Chen¹, Huijing Ye¹, Lai Wei¹, Huasheng Yang¹

Affiliations

¹ State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
² Ningxia Eye Hospital, People's Hospital of Ningxia Hui Autonomous Region, Ningxia Clinical Research Center of Blinding Eye Diseases, the First Clinical College of Northwest University for Nationalities, the Cooperative Teaching Hospital of North Minzu University, Yinchuan, Ningxia Hui Autonomous Region, China.
³ Department of Endocrinology and Diabetes Center, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

PMID: 30888403
DOI: 10.1210/jc.2018-01812

Abstract

Purpose: To investigate the change in IL-10-producing regulatory B cells (Breg), which suppress peripheral immune responses, in patients with thyroid-associated ophthalmopathy (TAO).

Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from healthy controls (n = 54), patients with Graves disease (n = 26), and patients with TAO (N=125), and stimulated with CpG/CD40L. The frequency of IL-10-producing Bregs and the expression of IL-10 in response to TSH stimulation were measured by flow cytometry. CD4+ T cells were cultured with Breg-depleted PBMCs to elucidate the function of Bregs in patients with TAO. The potential immunoregulatory mechanism was also investigated by Western blot and chromatin immunoprecipitation assays.

Results: Patients with active TAO had higher baseline levels of Bregs in their peripheral blood than both healthy controls and inactive patients. TSH promoted Bregs. Bregs from patients with TAO were defective in suppressing the activation of interferon (IFN)-γ+ and IL-17+ T cells in vitro.

Conclusions: Regulatory B cells in patients with TAO are functionally defective, suggesting that the defective Bregs might be responsible for the pathogenesis of TAO.