Deakin University
Browse

File(s) under permanent embargo

Batf3-dependent CD8 alpha(+) Dendritic Cells Aggravates Atherosclerosis via Th1 Cell Induction and Enhanced CCL5 Expression in Plaque Macrophages

journal contribution
posted on 2023-07-21, 03:50 authored by Yalin Li, Xueyan Liu, Wei DuanWei Duan, Hua Tian, Guangming Zhu, Hao He, Shutong Yao, Shuying Yi, Wengang Song, Hua Tang
Dendritic cells (DCs) play an important role in controlling T cell-mediated adaptive immunity in atherogenesis. However, the role of the basic leucine zipper transcription factor, ATF-like 3 (Batf3)-dependent CD8α+ DC subset in atherogenesis remains unclear. Here we show that Batf3-/-Apoe-/- mice, lacking CD8α+ DCs, exhibited a significant reduction in atherogenesis and T help 1 (Th1) cells compared with Apoe-/- controls. Then, we found that CD8α+ DCs preferentially induce Th1 cells via secreting interleukin-12 (IL-12), and that the expression of interferon-gamma (IFN-γ)or chemokine (C-C motif) ligand 5 (CCL5) in aorta were significantly decreased in Batf3-/-Apoe-/- mice. We further demonstrated that macrophages were the major CCL5-expressing cells in the plaque, which was significantly reduced in Batf3-/-Apoe-/- mice. Furthermore, we found CCL5 expression in macrophages was promoted by IFN-γ. Finally, we showed that Batf3-/-Apoe-/- mice displayed decreased infiltration of leukocytes in the plaque. Thus, CD8α+ DCs aggravated atherosclerosis, likely by inducing Th1 cell response, which promoted CCL5 expression in macrophages and increased infiltration of leukocytes and lesion inflammation.

History

Journal

EBIOMEDICINE

Volume

18

Pagination

188-198

Location

Netherlands

ISSN

2352-3964

eISSN

2352-3964

Language

English

Publisher

ELSEVIER SCIENCE BV