The Th17/Treg imbalance in patients with acute coronary syndrome

https://doi.org/10.1016/j.clim.2008.01.009Get rights and content

Abstract

Atherosclerosis is a chronic inflammatory disease regulated by T lymphocyte subsets. Recently, CD4+CD25+Foxp3+ regulatory T (Treg) cells and Th17 cells have been described as two distinct subsets from Th1 and Th2 cells and have the opposite effects on autoimmunity. Th17/Treg balance controls inflammation and may be important in the pathogenesis of plaque destabilization and the onset of acute coronary syndrome [ACS, including unstable angina (UA) and acute myocardial infarction (AMI)]. To assess whether this balance was broken in patients with coronary heart disease, we detected Th17/Treg functions on different levels including cell frequencies, related cytokine secretion and key transcription factors in patients with AMI, UA, stable angina (SA) and controls. The results demonstrated that patients with ACS revealed significant increase in peripheral Th17 number, Th17 related cytokines (IL-17, IL-6 and IL-23) and transcription factor (RORγt) levels and obvious decrease in Treg number, Treg related cytokines (IL-10 and TGF-β1) and transcription factor (Foxp3) levels as compared with patients with SA and controls. Results indicate that Th17/Treg functional imbalance exists in patients with ACS, suggesting a potential role for Th17/Treg imbalance in plaque destabilization and the onset of ACS.

Introduction

Atherosclerosis is a chronic inflammatory disease involving various immune cells, particularly T lymphocytes [1], [2], [3]. The up-regulation of T helper (Th)1 response has been shown in the local atherosclerotic lesions and circulating lymphocytes in an atherosclerotic animal model and patients with acute coronary syndrome [ACS, including unstable angina (UA) and acute myocardial infarction (AMI)], suggesting that Th1/Th2 imbalance plays an important role in plaque rupture and the onset of ACS [4], [5], [6], [7].

Recently, CD4+CD25+ regulatory T (Treg) cells and Th17 cells have been described as two distinct subsets from Th1 and Th2 cells. Treg cells expressing the forkhead/winged helix transcription factor (Foxp3) have an anti-inflammatory role and maintain tolerance to self components by contact-dependent suppression or releasing anti-inflammatory cytokines [interleukin (IL)-10 and transforming growth factor (TGF)-β1] [8], while Th17 cells expressing retinoic acid-related orphan receptor γt (RORγt) play critical roles in the development of autoimmunity and allergic reactions by producing IL-17 and, to a lesser extent, tumor necrosis factor (TNF)-αand IL-6 [9]. So the balance between Th17 and Treg may be important in the development/prevention of inflammatory and autoimmune diseases [10].

The objectives of this study were to evaluate whether the Th17/Treg balance was broken in patients with ACS.

Section snippets

Patients

This study conformed to the approved institutional guidelines. Informed consent was obtained from each patient. We studied 85 patients who underwent diagnostic catheterization (63 men and 22 women, mean age ± SD 59 ± 8 years). Patients were classified into 4 groups: (1) AMI group (20 men and 6 women, mean age 60 ± 7, inclusion criteria: myocardial infarction confirmed by significant rise of creatine kinase MB and troponin I levels); (2) UA group (12 men and 5 women, mean age 58 ± 9, inclusion criteria:

Basic clinical characteristics of patients

There were no significant differences in age, gender, number of diseased vessels, risk factors, medications among patients with AMI, UA and SA (Table 1).

Circulating Th17 frequencies increased in patients with ACS

As shown in Figure 1, the frequencies of Th17 (CD4+IL17+/CD4+ T cells) were markedly higher in patients with AMI (2.3 ± 1.3%) and UA (2.1 ± 1.1%) than those with SA (0.5 ± 0.3%) and CPS (0.3 ±0.2%) (P < 0.01), while there was no obvious difference between the SA and CPS group (P > 0.05).

Circulating Treg frequencies decreased in patients with ACS

As shown in Table 2 and Figure 2, the frequencies of CD4+CD25+ T

Discussion

Th17/Treg balance controls inflammation and may be important in the pathogenesis of plaque destabilization and the onset of ACS. To assess whether this balance was broken in patients with ACS, we detected Th17/Treg functions on different levels including cell frequencies, related cytokine secretion and key transcription factors. The results demonstrated that patients with ACS revealed significant increase in peripheral Th17 number, Th17 related cytokines (IL-17, IL-6 and IL-23) and

Sources of funding

The work described in this article was supported by the National Basic Research Program of China (973 Program): 2007CB512000; 2007CB512005 and the National Natural Science Foundation of China (No. 30600234).

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    Both authors contributed to the work equally.

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