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Curr Alzheimer Res. 2020 Feb 12. doi: 10.2174/1567205017666200212160343. [Epub ahead of print]

Amyloid β-induced Mesenteric Inflammation in an Alzheimer's Disease Transgenic Mouse Model.

Author information

1
Graduate School of Agricultural and Life Sciences, the University of Tokyo, Bunkyo-ku, Tokyo, Japan.
2
Central Laboratories for Key Technologies, Kirin Company Ltd, Yokohama-shi, Kanagawa, Japan.

Abstract

BACKGROUND:

Alzheimer's disease (AD) is a neurodegenerative disorder histopathologically characterized by the accumulation of amyloid β (Aβ) peptides and inflammation associated with activated microglia. These features are well investigated in the central nervous system using AD-model mice; however, peripheral inflammation in these mice has not been investigated well.

OBJECTIVE:

We evaluated the inflammatory responses, especially myeloid dendritic cells (mDCs), in peripheral lymphoid tissues in AD-model mice to determine their association with Aβ deposition.

METHODS:

We collected lymphocytes from mesenteric lymphoid nodes (MLNs) and Peyer's patches (PPs) of 5×FAD transgenic mice used as an AD model. Lymphocytes were analyzed using a flow cytometer to characterize mDCs and T cells. Collected lymphocytes were treated with Aβ1-42 ex vivo to evaluate the inflammatory response.

RESULTS:

We observed elevated levels of inflammatory cytokines and chemokines including interleukin (IL)-12 and macrophage inflammatory protein-1α in mDCs from MLNs and PPs and reduced levels of programmed death-ligand-1, an immunosuppressive co-stimulatory molecule, on the surface of mDCs from 5×FAD mice. Additionally, we found increases in interferon (IFN)-γ-producing CD4- or CD8- positive T cells in MLNs were increased in 5×FAD mice. Moreover, ex vivo treatment with Aβ peptides increased the production of IL-12 and IFN-γ by lymphocytes from 5×FAD mice.

CONCLUSION:

The present study showed that pro-inflammatory mDC and T cells were induced in MLNs and PPs of 5×FAD mice.

KEYWORDS:

Alzheimer's disease; Amyloid β; Mesenteric lymphoid node; Myeloid dendritic cells; Peyer's patch; T cells

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