title: 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.
authors: Department of Neurology, Affiliated Nanjing Brain Hospital, Nanjing Medical University, 264 Guangzhou Road, Nanjing, Jiangsu Province 210029, PR China.
authors: Jian-Quan
authors: JQ
authors: Shi
authors: Jun
authors: J
authors: Chen
authors: Bian-Rong
authors: BR
authors: Wang
authors: Yin-Wei
authors: YW
authors: Zhu
authors: Yan
authors: Y
authors: Xu
authors: Jun
authors: J
authors: Wang
authors: Hang
authors: H
authors: Xiao
authors: Jing-Ping
authors: JP
authors: Shi
authors: Ying-Dong
authors: YD
authors: Zhang
authors: Jun
authors: J
authors: Xu
mesh_terms: D016229:Amyloid beta-Peptides / Q000276:immunology* / Q000378:metabolism*; D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D004705:Endocytosis / Q000276:immunology / Q000502:physiology; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D008285:Major Histocompatibility Complex / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D014409:Tumor Necrosis Factor-alpha