Amyloid beta peptide promotes differentiation of pro-inflammatory human myeloid dendritic cells.
A key event of Alzheimer's disease (AD) pathogenesis is the production of amyloid beta peptides (A beta), which are hypothesized to lead to neurodegeneration by still unclear mechanisms, including a chronic inflammatory response characterized by innate immune cell activation and pro-inflammatory molecule release. Since dendritic cells (DCs) are central players of innate immune response and brain dendritic-like cells may have a crucial role in AD pathogenesis, this study investigates the effects of A beta on human DC functions. Myeloid DCs differentiated in the presence of A beta 42 showed an increase in survival and soluble antigen uptake, a reduction in HLA molecule expression and in IL-10 and IL-12 production. Accordingly, A beta 42-treated DCs were impaired in inducing T cell proliferation and IL-2 production. On the other hand, A beta 42 treatment provided DCs with the ability to release higher levels of IL-1 beta, IL-6 and IL-18, than control DCs. These results demonstrate that A beta 42 can modulate the immune system by inducing pro-inflammatory DC differentiation, thus gaining new insights into AD pathogenesis and immune-based therapeutic intervention.
Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Via Ardeatina 306, 00179 Rome, Italy. a.ciaramella@hsantalucia.it
Antonio
A
Ciaramella
Nunzia
N
Sanarico
Federica
F
Bizzoni
Maria Luisa
ML
Moro
Francesca
F
Salani
Giuseppe
G
Scapigliati
Gianfranco
G
Spalletta
Carlo
C
Caltagirone
Paola
P
Bossù
D016229:Amyloid beta-Peptides / Q000008:administration & dosage*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D022423:Myeloid Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D010446:Peptide Fragments / Q000008:administration & dosage*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)