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

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.