The Treg/Th17 Imbalance in Patients with Idiopathic Dilated Cardiomyopathy

Abstract

To assess whether Treg/Th17 balance was broken in patients with idiopathic dilated cardiomyopathy (DCM). We studied 25 patients who were diagnosed as idiopathic DCM (18 men and seven women, mean age 35.6 ± 5.2) and 25 normal persons (18 men and seven women, mean age 33.8 ± 4.9). Then, we detected Treg/Th17 functions on different levels including cell frequencies, related cytokine secretion and key transcription factors in patients with idiopathic DCM and controls. The results demonstrated that patients with idiopathic DCM revealed significant increase in peripheral Th17 number, Th17‐related cytokines (IL‐17, IL‐6, IL‐23) and transcription factor (RORγt) levels and obvious decrease in Treg number, Treg‐related cytokines (TGF‐β1 and IL‐10) and transcription factor (Foxp3) levels when compared to normal persons. Results indicated that Treg/Th17 functional imbalance existed in patients with idiopathic DCM, suggesting a potential role for Treg/Th17 imbalance in the development of idiopathic DCM.

Response Gene to Complement-32 Promotes the Imbalance of Treg/Th17 in Patients with Dilated Cardiomyopathy

“…On the other hand, the ratio of Treg/Th17 cells was lower in patients with DCM than that in healthy donors. These findings were in agreement with those of study from Wang et al [12]. Moreover, we demonstrated the elevation of RGC-32 levels was accompanied by the increased frequency of Th17 cells.…”

“…Interestingly, further work by Chen et al demonstrated that in autoimmune myocarditis a lower proportion of Treg cells was associated with a greater Th17 response and more severe autoimmune myocarditis [16]. An imbalance between Treg and Th17 cells has recently been observed in idiopathic DCM [12,17]. In the study by Rus et al, the proportion of Th17 was significantly decreased in RGC-32-deficient CD4 + T cells under Th17 polarizing conditions [18].…”

“…In this investigation, DCM was defined as systolic dysfunction [left ventricular ejection fraction (LVEF) < 45%] with ventricular dilation [left ventricular end-diastolic diameter (LVEDD) > 55 mm] in the absence of an apparent secondary cause of cardiomyopathy, such as coronary heart disease, hypertensive heart disease, or valvular heart disease [20]. The exclusion criteria included ischaemic cardiomyopathy, hypertrophic cardiomyopathy, hypertensive heart disease, a history of uncontrollable or untreated hypertension for at least a year before the documentation of LV Cellular Physiology and Biochemistry Cellular Physiology and Biochemistry dysfunction, and other secondary cardiomyopathies such as sarcoidosis and amyloidosis, the presence of significant coronary artery stenosis on angiography and non-ischaemic DCM secondary to valvular heart disease, systemic hypertension, cardiac surgery or acute myocarditis, excessive alcohol abuse, pregnancy, endocrine disease, active infectious disease or collagen disease, medical history of autoimmune disease [12,21]. All subjects gave written informed consent and the protocol was reviewed.…”

“…Th17 cells (mainly related cytokines IL-17, IL-22) account for pro-inflammatory immune responses but damaging tissue, and Treg cells (mainly related cytokines TGF-β1, IL-10) control inflammatory immune responses but hindering anti-inflammatory immunity. The mounting evidence indicates that two subsets of CD4 + T cells (i.e., Th17 and Treg cells) play an important role in the immunopathogenesis of inflammatory diseases, such as idiopathic DCM, MS, experimental autoimmune encephalomyelitis (EAE), and autoimmune thyroid diseases (AITDs) [12][13][14]. The work by Baldeviano et al suggested a pivotal role for IL-17 in the progression to DCM in an experimental autoimmune model of myocarditis in mice, promoting a fibrotic response [15].…”

Defective Circulating Regulatory B Cells in Patients with Dilated Cardiomyopathy

“…Tregs are decreased and have impaired functionality in DCM [26, 40]. Additionally, cardiac-specific auto-antibodies that have been reported in DCM patients showed a pathogenic role in cardiac dilatation and dysfunction.…”