Deletion of Batf3-dependent antigen-presenting cells does not affect atherosclerotic lesion formation in mice

Abstract

Atherosclerosis is the main underlying cause for cardiovascular events such as myocardial infarction and stroke and its development might be influenced by immune cells. Dendritic cells (DCs) bridge innate and adaptive immune responses by presenting antigens to T cells and releasing a variety of cytokines. Several subsets of DCs can be discriminated that engage specific transcriptional pathways for their development. Basic leucine zipper transcription factor ATF-like 3 (Batf3) is required for the development of classical CD8α+ and CD103+ DCs. By crossing mice deficient in Batf3 with atherosclerosis-prone low density lipoprotein receptor (Ldlr-/-)-deficient mice we here aimed to further address the contribution of Batf3-dependent CD8α+ and CD103+ antigen-presenting cells to atherosclerosis. We demonstrate that deficiency in Batf3 entailed mild effects on the immune response in the spleen but did not alter atherosclerotic lesion formation in the aorta or aortic root, nor affected plaque phenotype in low density lipoprotein receptor-deficient mice fed a high fat diet. We thus provide evidence that Batf3-dependent antigen-presenting cells do not have a prominent role in atherosclerosis.

Immunobiology of Atherosclerosis: A Complex Net of Interactions

“…However, CD103 + DC depletion in LDLR −/− Flt3 −/− mice shows the depletion of aortic Tregs and increased atherosclerosis [301]. Plaque size is unaffected in LDLR −/− mice reconstituted with Baft3 −/− bone marrow [302] and in LDLR −/− Batf3 −/− mice [303]. However, experiments in ApoE −/− Batf3 −/− mice support a proatherogenic role and elevated Th1 stimulation capacity for Batf3-dependent DCs [304].…”

The Evolving Role of Dendritic Cells in Atherosclerosis

“…To elucidate the role of cDC1s and cDC2s independently from each other, a number of approaches have been applied in mice to modulate the development and maintenance of individual DC subtypes [67,[113][114][115][116]. Table 4 summarizes the different approaches and the observed net effect on atherosclerosis development.…”

Dendritic Cells and T Cells, Partners in Atherogenesis and the Translating Road Ahead

“…Collectively, these data of CD103 + DC in other tissues lead to a hypothesis that vascular CD103 + DCs could also induce Treg differentiation and recruitment in early atherosclerotic lesions via TGF-β/retinoic acid or CCL22 pathways, respectively, which agrees with previous reports that vascular CD103 + DCs protect against atherosclerosis via Tregs (18). However, when the atherogenic roles of CD103 + DCs were assessed in mice deficient in their dependent transcription factor Batf3 in ApoE −/− mice, which also lacked CD103 + DCs, a significant reduction in atherogenesis via reduced Th1 cell induction and C-C motif ligand 5 (CCL5) expression were found (20), whereas mice deficient in the same transcription factor but crossed with Ldlr −/− mice demonstrated mild effects on the immune response in the spleen without altering atherosclerotic lesion formation and plaque phenotype (37). These conflicting results could be caused by different model specific pathologies in the development of atherosclerosis.…”