| First Author | Guillot-Sestier MV | Year | 2015 |
| Journal | Neuron | Volume | 85 |
| Issue | 3 | Pages | 534-48 |
| PubMed ID | 25619654 | Mgi Jnum | J:219701 |
| Mgi Id | MGI:5629598 | Doi | 10.1016/j.neuron.2014.12.068 |
| Citation | Guillot-Sestier MV, et al. (2015) Il10 deficiency rebalances innate immunity to mitigate Alzheimer-like pathology. Neuron 85(3):534-48 |
| abstractText | The impact of inflammation suppressor pathways on Alzheimer's disease (AD) evolution remains poorly understood. Human genetic evidence suggests involvement of the cardinal anti-inflammatory cytokine, interleukin-10 (IL10). We crossed the APP/PS1 mouse model of cerebral amyloidosis with a mouse deficient in Il10 (APP/PS1(+)Il10(-/-)). Quantitative in silico 3D modeling revealed activated Abeta phagocytic microglia in APP/PS1(+)Il10(-/-) mice that restricted cerebral amyloidosis. Genome-wide RNA sequencing of APP/PS1(+)Il10(-/-) brains showed selective modulation of innate immune genes that drive neuroinflammation. Il10 deficiency preserved synaptic integrity and mitigated cognitive disturbance in APP/PS1 mice. In vitro knockdown of microglial Il10-Stat3 signaling endorsed Abeta phagocytosis, while exogenous IL-10 had the converse effect. Il10 deficiency also partially overcame inhibition of microglial Abeta uptake by human Apolipoprotein E. Finally, the IL-10 signaling pathway was abnormally elevated in AD patient brains. Our results suggest that "rebalancing" innate immunity by blocking the IL-10 anti-inflammatory response may be therapeutically relevant for AD. |
