冠状动脉疾病患者各种脂肪组织库中的T调节性淋巴细胞和FoxP3核易位

I. Kologrivova, A. Dmitriukov, O. Kharitonova, E. Kravchenko, N. V. Naryzhnaya, O. Koshelskaya, T. Suslova
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引用次数: 0

摘要

脂肪组织中存在T调节性淋巴细胞(Treg)。它们在心外膜和胸腺脂肪组织中的频率以及FoxP3核易位水平仍未被研究。脂肪驻留Tregs的特性可能在冠状动脉疾病患者中作为动脉粥样硬化发展的潜在病理生理因素具有重要意义。本研究的目的是比较冠心病患者心外膜、胸腺、皮下脂肪组织和外周血中FoxP3+Tregs和FoxP3核易位的频率。我们对11例冠心病患者进行了一项初步研究,这些患者在事先进行选择性冠状动脉造影后计划行冠状动脉搭桥手术。采用显像流式细胞术评价外周血和心外膜、皮下及胸腺脂肪组织间质血管部分CD4+CD25hiFoxP3+、CD4+CD25loFoxP3+淋巴细胞及FoxP3核易位的频率。心外膜脂肪组织中CD4+CD25hiFoxP3+和CD4+CD25loFoxP3+淋巴细胞频率高于血液(分别高3倍和5倍,p = 0.020);皮下脂肪组织中CD4+CD25loFoxP3+细胞频率是血液中CD4+CD25loFoxP3+细胞频率的4倍(p = 0.028)。血液中FoxP3核易位水平最高,心外膜、皮下和胸腺脂肪组织中FoxP3核易位水平降低(CD4+CD25hiFoxP3+和CD4+CD25loFoxP3+淋巴细胞p = 0.020)。胸腺CD4+CD25loFoxP3+细胞频率与年龄直接相关(rs = 0.818;P = 0.002),心外膜脂肪组织呈负相关(rs = -0.618;P = 0.043)。皮下脂肪组织中CD4+CD25hiFoxP3+和CD4+CD25loFoxP3+与FoxP3核易位的频率与年龄呈负相关(rs = -0.827;P = 0.002, rs = -0.648;P = 0.031)。胸腺脂肪组织中携带FoxP3核易位的CD4+CD25loFoxP3+细胞的频率与腰臀比呈负相关(rs = -0.700;P = 0.016)。动脉粥样硬化的严重程度仅与皮下脂肪组织中CD4+CD25loFoxP3+细胞的频率有关(rs = -0.655;P = 0.029)。因此,心外膜和皮下脂肪组织富含Treg,但这些脂肪库中影响Treg积累和FoxP3核易位的因素可能不同。所得结果可进一步用于动脉粥样硬化患者的个体化免疫调节治疗。
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T regulatory lymphocytes and FoxP3 nuclear translocation in various adipose tissue depots in patients with coronary artery disease
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.
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来源期刊
Medical Immunology (Russia)
Medical Immunology (Russia) Medicine-Immunology and Allergy
CiteScore
0.70
自引率
0.00%
发文量
88
审稿时长
12 weeks
期刊介绍: The journal mission is to promote scientific achievements in fundamental and applied immunology to various medical fields, the publication of reviews, lectures, essays by leading domestic and foreign experts in the field of fundamental and experimental immunology, clinical immunology, allergology, immunodiagnostics and immunotherapy of infectious, allergy, autoimmune diseases and cancer.
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