1. Regulatory T cells delay disease progression in Alzheimer-like pathology.
- Author
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Dansokho, Cira, Ahmed, Dylla Ait, Aid, Saba, Toly-Ndour, Cécile, Chaigneau, Thomas, Calle, Vanessa, Cagnard, Nicolas, Holzenberger, Martin, Piaggio, Eliane, Aucouturier, Pierre, Dorothée, Guillaume, and Ait Ahmed, Dylla
- Subjects
T cells ,ALZHEIMER'S disease ,MICROGLIA ,AMYLOID ,IMMUNOTHERAPY ,ALZHEIMER'S disease prevention ,ANIMAL experimentation ,BRAIN ,INTERLEUKIN-2 ,LEARNING ,MEMBRANE proteins ,MICE ,PROTEIN precursors ,DISEASE progression ,PHYSIOLOGY - Abstract
Recent studies highlight the implication of innate and adaptive immunity in the pathophysiology of Alzheimer's disease, and foster immunotherapy as a promising strategy for its treatment. Vaccines targeting amyloid-β peptide provided encouraging results in mouse models, but severe side effects attributed to T cell responses in the first clinical trial AN1792 underlined the need for better understanding adaptive immunity in Alzheimer's disease. We previously showed that regulatory T cells critically control amyloid-β-specific CD4(+) T cell responses in both physiological and pathological settings. Here, we analysed the impact of regulatory T cells on spontaneous disease progression in a murine model of Alzheimer's disease. Early transient depletion of regulatory T cells accelerated the onset of cognitive deficits in APPPS1 mice, without altering amyloid-β deposition. Earlier cognitive impairment correlated with reduced recruitment of microglia towards amyloid deposits and altered disease-related gene expression profile. Conversely, amplification of regulatory T cells through peripheral low-dose IL-2 treatment increased numbers of plaque-associated microglia, and restored cognitive functions in APPPS1 mice. These data suggest that regulatory T cells play a beneficial role in the pathophysiology of Alzheimer's disease, by slowing disease progression and modulating microglial response to amyloid-β deposition. Our study highlights the therapeutic potential of repurposed IL-2 for innovative immunotherapy based on modulation of regulatory T cells in Alzheimer's disease. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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