Batf3-dependent CD8α+ Dendritic Cells Aggravates Atherosclerosis via Th1 Cell Induction and Enhanced CCL5 Expression in Plaque Macrophages

EBioMedicine

Hao He¹  Guangming Zhu¹  Shuying Yi¹  Xueyan Liu¹  Yalin Li¹  Wengang Song¹  Wei Duan¹  Hua Tang¹  Hua Tian²  Shutong Yao² 

[1] Institute of Immunology, Taishan Medical University, Taian, Shandong, China;Key Laboratory of Atherosclerosis in Universities of Shandong and Institute of Atherosclerosis, Taishan Medical University, Shandong, China;

关键词: Batf3;    CD8α+ DCs;    Th1 cells;    CCL5;    Atherosclerosis;   

DOI  :  10.1016/j.ebiom.2017.04.008

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown