Regulatory T cells decrease A1‐like C3‐positive reactive astrocytes in Alzheimer‐like pathology

Background Increasing evidence support a key role of peripheral immune processes in the pathophysiology Alzheimer’s disease (AD), highlighting an intricate interplay between brain resident glial cells and both innate adaptive effectors. We previously showed that regulatory T (Tregs) have beneficial impact on progression AD-like pathology, notably by modulating microglial response associated with Ab deposits mouse model amyloid pathology. Besides microglia, reactive astrocytes also play critical neuroinflammatory AD. Different phenotypes recently been characterized, including A1 neurotoxic A2 neuroprotective subtypes. However, precise Tregs astrocyte reactivity AD still remains poorly defined. Methods assessed Treg immunomodulation Using 3D imaging we carried out extensive morphological analyses following either depletion or amplification Tregs. further expression several A1- A2-like markers immunofluorescence RT-qPCR. Results Modulation did not significantly magnitude global nor close vicinity cortical deposits. observe changes number, morphology, branching complexity according to early transient modulated balance subtypes, resulting increased C3-positive A1-like Conversely, decreased larger Intriguingly, modulation impacted cerebral subsets healthy mice. Conclusions Our study suggests contribute modulate fine tune subtypes dampening favor phenotypes. This effect may partly relate their capacity at steady state homeostasis. data highlight need for refined strategy analysis better deciphering neurodegeneration.