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

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.

Systemic review and meta‐analysis of the association between interleukin‐10 and Takayasu arteritis

“…There was no significant differences between the 2 groups ( I 2 = 87%, P > 0.05, Figure 2, upper panel). Three studies compared the IL‐10 levels in active and stable TAK patients 5,13,17 . Among those studies, 109 cases were active in TAK and 143 cases were in stable stage.…”

“…After this preliminary screening, 17 studies were selected through screening the full text. According to the inclusion and exclusion criteria, 7 studies were eventually selected for the meta-analysis 5,[12][13][14][15][16][17] (Figure 1).…”

“…Three studies compared the IL-10 levels in active and stable TAK patients. 5,13,17 Among those studies, 109 cases were active in TAK and 143 cases were in stable stage. The levels of IL-10 were lower in the active group than those in stable group (SMD = −0.47, 95% CI: −0.93, 0.00, I 2 = 87%, P = 0.05, Figure 2, lower panel).…”

Vasculitogenic T Cells in Large Vessel Vasculitis

“…This increase may stem from overactivation of the NOTCH1-mTOR pathway ( 88 , 89 ) and/or an increase in the number of CD4 + IL-21-producing T cells ( 89 , 90 ). In parallel, a decrease in CD4 + Treg numbers has also been documented ( 91 ). In contrast, unlike GCA, microarray analysis has demonstrated that the Tfh signature that includes CXCR5 and CCR6 is significantly increased in the blood and the aorta ( 62 ).…”

Medium-vessel and large-vessel vasculitis in children

“…The pathogenesis of Takayasu arteritis is still relatively poorly understood. The elucidation of pathogenic role of T lymphocytes as the source of interferon-g (IFN-g) and the specific role of novel TH-17 sub-populations (Th17.1 and PD1þTh17) combined with reduced peripheral regulatory T cells as well as specific gene signatures for follicular helper T cells in the circulation and aortic tissue of patients with Takayasu arteritis offer insights into the pathogenesis of Takayasu arteritis [13][14][15][16][17]. Macrophage subpopulations in the aortic tissues of patients with Takayasu arteritis have also been reported on in two recent studies [18,19].…”