The emerging role of Th1 cells in atherosclerosis and its implications for therapy

Abstract

Atherosclerosis is a chronic progressive inflammatory disease of the large and medium-sized artery walls. The molecular mechanisms regulating the onset and progression of atherosclerosis remain unclear. T cells, one of the most common immune cell types in atherosclerotic plaques, are increasingly recognized as a key mediator in the pathogenesis of atherosclerosis. Th1 cells are a subset of CD4+ T helper cells of the adaptive immune system, characterized by the expression of the transcription factor T-bet and secretion of cytokines such as IFN-γ. Converging evidence shows that Th1 cells play a key role in the onset and progression of atherosclerosis. Besides, Th1 is the central mediator to orchestrate the adaptive immune system. In this review, we aim to summarize the complex role of Th1 cells in atherosclerosis and propose novel preventative and therapeutic approaches targeting Th1 cell-associated specific cytokines and receptors to prevent atherogenesis.

Oxidized low‐density lipoproteins impair the pro‐atherosclerotic effect of granulocyte‐macrophage‐colony‐stimulating factor‐producing T helper cells on macrophages

“…Besides, oxLDL enhances Th1 differentiation while suppressing Th2 differentiation and Th1 cells promote atherosclerosis progression. 4,15 Accordingly, oxLDL still exacerbates atherosclerosis development regardless of its effect on ThGM cells. Furthermore, although oxLDL could suppress ThGM cell function, inflammatory cells in atherosclerotic aortas such as macrophages and dendritic cells would produce proinflammatory mediators to counteract the effect of oxLDL and consequently keep or enhance the pathogenicity of ThGM cells.…”

“…We hypothesize that oxLDL's atherosclerosis‐inducing effect on macrophages overwhelms its suppressive impact on ThGM cells. Besides, oxLDL enhances Th1 differentiation while suppressing Th2 differentiation and Th1 cells promote atherosclerosis progression 4,15 . Accordingly, oxLDL still exacerbates atherosclerosis development regardless of its effect on ThGM cells.…”

“…Th1 and Th17 cells trigger chronic inflammation in atherosclerotic lesions to facilitate foam cell formation and plaque progression. [3][4][5][6][7][8] A novel helper T cell population, featuring significant production of granulocyte macrophagecolony-stimulating factor (GM-CSF) and little expression of IFN-γ, IL-17, T-box expressed in T cells (T-bet), GATA binding protein 3 (GATA3), retinoic acid-related orphan receptor gamma t (RORγt) and forkhead box P3 (Foxp3), was discovered about 10 years ago. 9,10 Termed GM-CSF-producing T helper (ThGM) cells, this cell population reinforces the function of other T cell subsets.…”

“…Educated by antigen‐presenting cells and cytokines, CD4 + T cells differentiate into effector helper T cells, including T helper 1 (Th1), T helper 2 (Th2) and T helper 17 (Th17) cells. Th1 and Th17 cells trigger chronic inflammation in atherosclerotic lesions to facilitate foam cell formation and plaque progression 3–8 . A novel helper T cell population, featuring significant production of granulocyte macrophage‐colony‐stimulating factor (GM‐CSF) and little expression of IFN‐γ, IL‐17, T‐box expressed in T cells (T‐bet), GATA binding protein 3 (GATA3), retinoic acid‐related orphan receptor gamma t (RORγt) and forkhead box P3 (Foxp3), was discovered about 10 years ago 9,10 .…”

T Cells in Atherosclerosis: Key Players in the Pathogenesis of Vascular Disease

“…Within the lesional T helper cell subsets, T H 1 cells are the predominant T cell subtype found in both human and mouse atherosclerotic plaques [12]. It is widely believed that T H 1 cells promote inflammation, plaque instability, and lesion growth within atherosclerosis [55]. Genetic deficiency of the T H 1 lineage-specific transcription factor, TBX21 (T-bet), as well as genetic deficiency of IFN-y reduced atherosclerosis in hyperlipidemic mice, suggesting a pro-atherogenic role [56,57].…”