The Pivotal Role of Thymus in Atherosclerosis Mediated by Immune and Inflammatory Response

Abstract

Atherosclerosis is one kind of chronic inflammatory disease, in which multiple types of immune cells or factors are involved. Data from experimental and clinical studies on atherosclerosis have confirmed the key roles of immune cells and inflammation in such process. The thymus as a key organ in T lymphocyte ontogenesis has an important role in optimizing immune system function throughout the life, and dysfunction of thymus has been proved to be associated with severity of atherosclerosis. Based on previous research, we begin with the hypothesis that low density lipoprotein or cholesterol reduces the expression of the thymus transcription factor Foxn1 via low density lipoprotein receptors on the membrane surface and low density lipoprotein receptor related proteins on the cell surface, which cause the thymus function decline or degradation. The imbalance of T cell subgroups and the decrease of naive T cells due to thymus dysfunction cause the increase or decrease in the secretion of various inflammatory factors, which in turn aggravates or inhibits atherosclerosis progression and cardiovascular events. Hence, thymus may be the pivotal role in coronary heart disease mediated by atherosclerosis and cardiovascular events and it can imply a novel treatment strategy for the clinical management of patients with atherosclerosis in addition to different commercial drugs. Modulation of immune system by inducing thymus function may be a therapeutic approach for the prevention of atherosclerosis. Purpose of this review is to summarize and discuss the recent advances about the impact of thymus function on atherosclerosis by the data from animal or human studies and the potential mechanisms.

The role of the thymus in COVID-19 disease severity: implications for antibody treatment and immunization

“…Immune changes that occur with thymic aging (immune senescence) lead to an inflammatory environment that underlies the pathogenesis of diseases of aging (i.e. cardiovascular disease, hypertension, chronic obstructive lung disease and arthritis), [1][2][3][4] and people who develop these comorbidities are known to be at higher risk for severe COVID-19 infection and death. 5,6 Although knowledge of the thymus has existed since the time of the ancient Greeks (130-200 AD), who called the thymus thumos, meaning "principle of life," or "heart, soul, passion, life" 7 there were few efforts to understand its function until the 1960s when removal of the thymus in a mouse model was shown to lead to immune deficiency.…”

“…49 As the productive capacity of the thymus lags, the frequency of naïve T cell production is reduced and the TCR repertoire contracts. 1 In young and even middle-aged adults, the naïve CD45RA+CD62L+CD4 positive T cell repertoire diversity has been estimated at 20 million different TCR-β chains; in the Table 1. The effect of aging on thymus cytokine production.…”

“…Immune changes that occur with thymic aging (immune senescence) lead to an inflammatory environment that underlies the pathogenesis of diseases of aging (i.e. cardiovascular disease, hypertension, chronic obstructive lung disease and arthritis), 1–4 and people who develop these comorbidities are known to be at higher risk for severe COVID-19 infection and death. 5 , 6 …”

“…As the productive capacity of the thymus lags, the frequency of naïve T cell production is reduced and the TCR repertoire contracts. 1 In young and even middle‐aged adults, the naïve CD45RA+CD62L+CD4 positive T cell repertoire diversity has been estimated at 20 million different TCR‐β chains; in the elderly (older than 70 years), 50 the pool has severely contracted to 200,000 TCR‐β specificities. 51 The 95% decline in TCR repertoire diversity in CD4 + T cells in the elderly may limit functional response.…”

Cyclooxygenases and the cardiovascular system

“…Firstly, COX-2 is expressed selectively in medullary epithelial cells of the human thymus where it may influence immature CD4 + and CD8 + thymocytes (Rocca, et al, 2002). Secondly, immune cell regulation by the thymus is important in atherosclerosis (Dai, Zhang, Wang, Wu, & Liang, 2018;Tse, Tse, Sidney, Sette, & Ley, 2013). Thirdly, COX-2 knockout mice have increased atherosclerosis associated with accumulation of T-lymphocytes in atherosclerotic plaques (Kirkby, et al, 2014).…”