Infiltrating CD8+ T cells exacerbate Alzheimer’s disease pathology in a 3D human neuroimmune axis model
Brain infiltration of peripheral immune cells and their interactions with brain-resident cells may contribute to Alzheimer’s disease (AD) pathology. To examine these interactions, in the present study we developed a three-dimensional human neuroimmune axis model comprising stem cell-derived neurons,...
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Veröffentlicht in: | Nature neuroscience 2023-09, Vol.26 (9), p.1489-1504 |
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Sprache: | eng |
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Zusammenfassung: | Brain infiltration of peripheral immune cells and their interactions with brain-resident cells may contribute to Alzheimer’s disease (AD) pathology. To examine these interactions, in the present study we developed a three-dimensional human neuroimmune axis model comprising stem cell-derived neurons, astrocytes and microglia, together with peripheral immune cells. We observed an increase in the number of T cells (but not B cells) and monocytes selectively infiltrating into AD relative to control cultures. Infiltration of CD8
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T cells into AD cultures led to increased microglial activation, neuroinflammation and neurodegeneration. Using single-cell RNA-sequencing, we identified that infiltration of T cells into AD cultures led to induction of interferon-γ and neuroinflammatory pathways in glial cells. We found key roles for the C-X-C motif chemokine ligand 10 (CXCL10) and its receptor, CXCR3, in regulating T cell infiltration and neuronal damage in AD cultures. This human neuroimmune axis model is a useful tool to study the effects of peripheral immune cells in brain disease.
Jorfi et al. developed a three-dimensional human neuroimmune axis model of Alzheimer’s disease (AD). The authors demonstrated an increase in T cell infiltration into AD cultures, which led to microglial activation and exacerbation of neurodegeneration. |
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ISSN: | 1097-6256 1546-1726 1546-1726 |
DOI: | 10.1038/s41593-023-01415-3 |