
C-C 趨化因子受體 4 (CCR4) 缺乏會損害調節性 T 細胞 (Treg) 功能和向動脈粥樣硬化病灶的遷移，從而促進促炎性 Th1 細胞反應並加劇小鼠的早期動脈粥樣硬化。


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Chronic inflammation via dysregulation of T cell immune responses is critically involved in the pathogenesis of atherosclerotic cardiovascular disease. Improving the balance between proinflammatory T cells and anti-inflammatory regulatory T cells (Tregs) may be an attractive approach for treating atherosclerosis. Although C-C chemokine receptor 4 (CCR4) has been shown to mediate the recruitment of T cells to inflamed tissues, its role in atherosclerosis is unclear. Here, we show that genetic deletion of CCR4 in hypercholesterolemic mice accelerates the development of early atherosclerotic lesions characterized by an inflammatory plaque phenotype. This was associated with proinflammatory T helper type 1 (Th1) cell-skewed responses in peripheral lymphoid tissues, para-aortic lymph nodes, and atherosclerotic aorta. Mechanistically, CCR4 deficiency in Tregs impaired their suppressive function and migration to the atherosclerotic aorta and augmented Th1 cell-mediated immune responses through defective regulation of dendritic cell function, which accelerated aortic inflammation and atherosclerotic lesion development. Thus, we revealed a previously unrecognized role for CCR4 in controlling the early stage of atherosclerosis via Treg-dependent regulation of proinflammatory T cell responses. Our data suggest that CCR4 is an important negative regulator of atherosclerosis.

### Competing Interest Statement

The authors have declared no competing interest.

C-C 趨化因子受體 4 缺乏症加劇小鼠早期動脈粥樣硬化