Decreased Absolute Number of Circulating Regulatory T Cells in Patients With Takayasu's Arteritis.

Wen Jia,Jian-Ping Cao,Jing Luo,Yan-Liu Yan-Liu,Jian-Fang Xie,Xiao-Feng Li,Cheng-Lan Yan,Chong Gao,Guang-Ying Liu,Zi-Li Fu,Xia Wang

doi:10.3389/fimmu.2021.768244

Abstract

BackgroundTakayasu’s arteritis (TA) is a type of primary large vessel vasculitis. Th1, Th17, and Tfh cells have been reported to be associated with TA relapse. However, the relationship between regulatory T cells (Tregs) and TA remains unclear.ObjectiveTo analyze the levels of circulating lymphocytes, especially Treg cells (CD4+CD25+FOXP3+ T cells) and serum cytokines in TA patients and explore their relationship with their changes and TA disease activity.MethodsA total of 57 TA patients and 43 sex- and age-matched healthy controls (HCs) were enrolled. According to NIH standards, 36 patients had active disease status. Flow cytometry combined with counting was used to detect the absolute numbers and ratios of Th1, Th2, Th17, and Treg cells in the peripheral blood of all the subjects. Magnetic bead-based multiplex immunoassay was used to detect cytokines.ResultsCompared to HCs, the absolute number and proportion of peripheral Treg cells in TA patients was significantly decreased, while Th17 cells were significantly increased. Furthermore, compared to the inactive group, the TA active group had significantly increased levels of interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α, but lower IL-10 levels. The absolute number of Th2 cells was negatively associated with platelet (PLT) and NIS scores in TA patients. The proportion of Th2 cells was negatively associated with the erythrocyte sedimentation rate in TA patients. After treatment, Treg cells were markedly increased.ConclusionThere was a Th17-Treg cell imbalance with a significant reduction in peripheral Treg cells and an increase in Th17 cells in TA patients compared to the HCs. The levels of IL-6, IL-10, IL-17, and TNF-α appeared to be related to disease activity.

Highlights

Takayasu’s arteritis (TA), a primary large vessel vasculitis, causes chronic, progressive, and non-specific inflammation of the aorta and its main branches, and stenosis and occlusion of various arteries, which leads to ischemic manifestations
We observed a significant decline in the absolute numbers and proportion of peripheral CD4+ Treg cells in the TA patients compared to the healthy controls (HCs) (30.2 ± 14.2 vs 37.1 ± 9.2 cells/ μl, p = 0.001; 3.4 ± 1.6% vs 5.5 ± 1.1%, p
We demonstrated that the absolute number of circulating Treg cells was significantly lower in the TA patients, even in the inactive group, than in the HCs, which suggests that the Treg cell reduction may be involved in disease onset

Summary

Introduction

Takayasu’s arteritis (TA), a primary large vessel vasculitis, causes chronic, progressive, and non-specific inflammation of the aorta and its main branches, and stenosis and occlusion of various arteries, which leads to ischemic manifestations. Infiltration of a variety of inflammatory cells in the blood-vessel walls is the main pathological manifestation of TA. Recent studies have demonstrated that Th17 cells are upregulated in TA and play an important role in its pathogenesis [3, 4]. Regulatory T cells (Tregs) are the key anti-inflammatory cells of the immune response. Zhang et al [5] found that overactivation of mTORC1 in TA patients can upregulate the expression of Th1 and Th17 cells. The expression of CD8+ Treg remained normal. Takayasu’s arteritis (TA) is a type of primary large vessel vasculitis. The relationship between regulatory T cells (Tregs) and TA remains unclear

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