SLAM/SAP Decreased Follicular Regulatory T Cells in Patients with Graves' Disease.

Lina Geng,Yingzhao Liu,Shengjun Wang,Xinyi Tang,Zhigang Hu,Jun Yang,Huiyong Peng,Jie Tian,Huaxi Xu,Lihua Duan

doi:10.1155/2021/5548463

Abstract

Signaling lymphocytic activation molecule (SLAM) and SLAM-associated protein (SAP) play important role in inflammatory and autoimmune diseases. Our study is aimed at detecting the expression of SLAM and SAP in patients with Graves' disease (GD) and analyzing the effect of SLAM/SAP on circulating blood CD4+CXCR5+Foxp3+ follicular regulatory T (Tfr) cells. The level of SAP in CD4+CXCR5+ T cells and the level of SLAM on CD19+ B cells were significantly increased in the patients with GD, but no significant difference in the level of SLAM on CD4+CXCR5+ T cells was observed between the patients with GD and the healthy controls. A decrease in the percentage of Foxp3+ cells in CD4+CXCR5+ T cells was observed following anti-SLAM treatment, but the percentages of IFN-γ+ cells, IL-4+ cells, and IL-17+ cells showed no obvious differences. The proportion of circulating Tfr cells was decreased in the patients with GD, and the proportion of circulating Tfr cells had a negative correlation with the level of SAP in CD4+CXCR5+ T cells and the levels of autoantibodies in the serum of the patients with GD. Our results suggested that the SLAM/SAP signaling pathway is involved in the decrease of circulating Tfr cells in Graves' disease.

Highlights

Graves’ disease (GD) is an organ-specific autoimmune disease with a complex pathogenesis that involves aberrant B and T lymphocyte responses
Many studies have reported that signaling lymphocytic activation molecule (SLAM) or SLAM-associated protein (SAP) is elevated in some autoimmune diseases; we investigated whether the expression of these two molecules is changed in patients with GD
It has been reported that SLAM or SAP is increased in autoimmune diseases [32,33,34], and we investigated whether SLAM and SAP would be increased in GD

Summary

Introduction

Graves’ disease (GD) is an organ-specific autoimmune disease with a complex pathogenesis that involves aberrant B and T lymphocyte responses. TR-Ab, whose positive rate in patients with untreated GD is as high as 85-100%, interacts with the TSH receptor to stimulate thyroid follicular cell hyperplasia and promote thyroid hormone synthesis and secretion [1]. Many studies have shown that Th1, Th2, and Th17 cells, which are subtypes of CD4+ T cells, are effector helper T cells that participate in the pathogenesis of Graves’ disease [2,3,4]. We recently found that follicular helper T (Tfh) cells are involved in the pathogenesis of this disease [5, 6]. Our previous studies showed that the percentage of circulating Tfh cells in patients with GD was increased, which is related to the disease process [5], but the molecules and mechanisms involved in this process are unclear

Methods

Results

Conclusion