Anti‐atherogenic peptide Ep1.B derived from apolipoprotein E induces tolerogenic plasmacytoid dendritic cells

Summary Tolerogenic dendritic cells (DCs) play a critical role in the induction of regulatory T cells (Tregs), which in turn suppress effector T cell responses. We have previously shown the induction of DCs from human and mouse monocytic cell lines, mouse splenocytes and human peripheral blood monocytes by a novel apolipoprotein E (ApoE)‐derived self‐peptide termed Ep1.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 Ep1.B from monocytic cell lines and from the bone marrow‐derived cells. We found Ep1.B treatment induced cells that showed characteristics of plasmacytoid dendritic cells (pDC). We explored in‐vitro and in‐vivo effects of Ep1.B‐induced DCs 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 Ep1.B‐induced pDCs promote the generation of Treg cells, and these cells contribute to the induction of peripheral tolerance in adaptive immunity and potentially contribute its anti‐atherogenic activity.