
C-Cケモカイン受容体4（CCR4）は、制御性T細胞（Treg）の動脈壁への遊走と炎症性Th1細胞応答の抑制を媒介することで、アテローム性動脈硬化症の初期段階を抑制する重要な役割を果たしている。


coremsg

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 chemokine receptor 4 deficiency exacerbates early atherosclerosis in mice

c-cケモカイン受容体4の欠損は-マウスの初期アテローム性動脈硬化症を悪化させる-


C-Cケモカイン受容体4の欠損は、マウスの初期アテローム性動脈硬化症を悪化させる
