Anti-atherogenic peptide Ep1.B derived from apolipoprotein E induces tolerogenic plasmacytoid dendritic cells.
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.
Centre for Human Immunology, Department of Microbiology and Immunology, Robarts Research Institute, University of Western Ontario, London, ON, Canada.
S M
SM
Bellemore
E
E
Nikoopour
B C Y
BC
Au
O
O
Krougly
E
E
Lee-Chan
S M
SM
Haeryfar
B
B
Singh
D019264:Adoptive Transfer; D000818:Animals; D001057:Apolipoproteins E / Q000008:administration & dosage / Q000494:pharmacology*; D039521:CD11c Antigen / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects*; D016130:Immunophenotyping; D007274:Injections, Intraperitoneal; D016898:Interferon-alpha / Q000096:biosynthesis; D051379:Mice; D016688:Mice, Inbred NOD; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D010641:Phenotype; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000276:immunology
D001057:Apolipoproteins E; D039521:CD11c Antigen; D016898:Interferon-alpha; D010446:Peptide Fragments; C524718:apolipoprotein E (239-252), mouse
apolipoprotein E; atherosclerosis; immunomodulation; peptides; plasmacytoid dendritic cells