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Regulatory T cells delay disease progression in Alzheimer-like pathology

2016; Oxford University Press; Volume: 139; Issue: 4 Linguagem: Inglês

10.1093/brain/awv408

1460-2156

Cira Dansokho, Dylla Ait Ahmed, Saba Aïd, Cécile Toly‐Ndour, Thomas Chaigneau, Vanessa Calle, Nicolas Cagnard, Martin Holzenberger, Eliane Piaggio, Pièrre Aucouturier, Guillaume Dorothée,

Tryptophan and brain disorders

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. Increasing data implicate adaptive immunity in Alzheimer's disease pathophysiology, but its involvement remains poorly defined. Using a mouse model, Dansokho et al. show that regulatory T cells slow cognitive decline and modulate the microglial response to amyloid deposition. The results support the therapeutic potential of regulatory T cell-based immunotherapy.