Short amyloid-beta immunogens show strong immunogenicity and avoid stimulating pro-inflammatory pathways in bone marrow-derived dendritic cells from C57BL/6J mice in vitro

Abstract

Amyloid beta peptide 1–15 (Aβ1–15) and its derivatives have attracted the attention of the scientific community as candidate vaccines for Alzheimer's disease (AD) immunotherapy. Recent studies suggested that Aβ1–42 modulated the immune system by inducing pro-inflammatory dendritic cells (DCs) with reduced antigen-presenting function. However, it remains elusive how Aβ1–15 impacts DCs function. We therefore investigated the modulation by short Aβ peptides of DCs from C57Bl/6J mice. Two new immunogens, a tandem repeat of two-lysine-linked Aβ1–15 sequences with or without an addition of a RGD motif, were tested. Chemotaxis, endocytosis, antigen presenting function and producing cytokines were measured. Both peptides increased migration/endocytosis of immature DCs and MHC II molecule expression/alloreactive T cell activation in TNF-α-matured DCs. In addition, they exhibited decreased production of Th1/Th2 cytokines and pro-inflammatory cytokines. Overall, the two peptides demonstrated strong immunogenicity but did not stimulate pro-inflammatory pathways. These results support the use of short Aβ immunogens in AD immunotherapy.