| RRC ID |
85678
|
| 著者 |
Tanaka T, Sasaki N, Krisnanda A, Amin HZ, Ito K, Horibe S, Matsuo K, Hirata KI, Nakayama T, Rikitake Y.
|
| タイトル |
C-C chemokine receptor 4 deficiency exacerbates early atherosclerosis in mice.
|
| ジャーナル |
Elife
|
| Abstract |
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 the augmentation of proinflammatory T helper type 1 (Th1) cell responses in peripheral lymphoid tissues, para-aortic lymph nodes, and atherosclerotic aorta. Mechanistically, CCR4 deficiency in Tregs impaired their suppressive function and tended to inhibit their migration to the atherosclerotic aorta, and subsequently 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.
|
| 巻・号 |
13
|
| 公開日 |
2025-7-3
|
| DOI |
10.7554/eLife.101830
|
| PII |
101830
|
| PMID |
40608058
|
| PMC |
PMC12226018
|
| MeSH |
Animals
Aorta / pathology
Atherosclerosis* / genetics
Atherosclerosis* / immunology
Atherosclerosis* / pathology
Dendritic Cells / immunology
Disease Models, Animal
Mice
Mice, Inbred C57BL
Mice, Knockout
Receptors, CCR4* / deficiency
Receptors, CCR4* / genetics
T-Lymphocytes, Regulatory / immunology
Th1 Cells / immunology
|
| IF |
7.08
|
| リソース情報 |
| 実験動物マウス |
RBRC05737 |
