T regulatory lymphocytes and FoxP3 nuclear translocation in various adipose tissue depots in patients with coronary artery disease

Abstract

T regulatory lymphocytes (Treg) are present is adipose tissue. Their frequency, as well as the level of FoxP3 nuclear translocation, in epicardial and thymus adipose tissue remains unexplored. Properties of adiposeresident Tregs may be of high significance in patients with coronary artery disease as potential pathophysiological factor in the development of atherosclerosis. The aim of the study was to compare frequency of FoxP3+Tregs and FoxP3 nuclear translocation in epicardial, thymus, subcutaneous adipose tissue and peripheral blood in patients with coronary artery disease. A pilot study was conducted in 11 patients with coronary artery disease scheduled for the coronary artery bypass graft surgery after prior selective coronary angiography. Frequency of CD4+CD25hiFoxP3+ and CD4+CD25loFoxP3+ lymphocytes and FoxP3 nuclear translocation were evaluated by imaging flow cytometry in peripheral blood and in stromal vascular fraction of epicardial, subcutaneous and thymus adipose tissue. Frequencies of CD4+CD25hiFoxP3+ and CD4+CD25loFoxP3+ lymphocytes were higher in epicardial adipose tissue compared to blood (3 and 5 times higher, p = 0.020); CD4+CD25loFoxP3+ cells frequency in subcutaneous adipose tissue was 4 times higher than in blood (p = 0.028). The level of FoxP3 nuclear translocation was the highest in blood and decreased in epicardial, subcutaneous and thymus adipose tissue (p = 0.020 both for CD4+CD25hiFoxP3+ and CD4+CD25loFoxP3+ lymphocytes). Frequency of CD4+CD25loFoxP3+ cells was directly related to age in thymus (rs = 0.818; p = 0.002), and inversely in epicardial adipose tissue (rs = -0.618; p = 0.043). Frequencies of CD4+CD25hiFoxP3+ and CD4+CD25loFoxP3+ with FoxP3 nuclear translocation in subcutaneous adipose tissue negatively correlated with age (rs = -0.827; p = 0.002 and rs = -0.648; p = 0.031, respectively). Frequency of CD4+CD25loFoxP3+ cells with FoxP3 nuclear translocation in thymus adipose tissue negatively correlated with waist-to-hip ratio (rs = -0.700; p = 0.016). The severity of atherosclerosis was related only to the frequency of CD4+CD25loFoxP3+ cells in subcutaneous adipose tissue (rs = -0.655; p = 0.029). Thus, epicardial and subcutaneous adipose tissue are enriched with Tregs, but factors that influence Treg accumulation and FoxP3 nuclear translocation in these fat depots may be different. The obtained results may further be used for personalized immunomodulatory therapy in patients with atherosclerosis.