Anti‐atherogenic peptide E p1. B derived from apolipoprotein E induces tolerogenic plasmacytoid dendritic cells

Summary Tolerogenic dendritic cells ( DC s) play a critical role in the induction of regulatory T cells ( T regs ), which in turn suppress effector T cell responses. We have previously shown the induction of DC s from human and mouse monocytic cell lines, mouse splenocytes and human peripheral blood monocytes by a novel apolipoprotein E ( ApoE )‐derived self‐peptide termed E p1. B . We also showed that this C ‐terminal region 239–252 peptide of ApoE has strong anti‐atherogenic activity and reduces neointimal hyperplasia after vascular surgery in rats and wild‐type as well as ApoE ‐deficient mice. In this study, we explored the phenotype of DC subset induced by E p1. B from monocytic cell lines and from the bone marrow‐derived cells. We found E p1. B treatment induced cells that showed characteristics of plasmacytoid dendritic cells (p DC ). We explored in‐vitro and in‐vivo effects of E p1. B ‐induced DC s on antigen‐specific T cell responses. Upon in‐vivo injection of these cells with antigen, the subsequent ex‐vivo antigen‐specific proliferation of lymph node cells and splenocytes from recipient mice was greatly reduced. Our results suggest that E p1. B ‐induced p DC s promote the generation of T reg cells, and these cells contribute to the induction of peripheral tolerance in adaptive immunity and potentially contribute its anti‐atherogenic activity.