| First Author | Jorfi M | Year | 2023 |
| Journal | Nat Neurosci | Volume | 26 |
| Issue | 9 | Pages | 1489-1504 |
| PubMed ID | 37620442 | Mgi Jnum | J:350080 |
| Mgi Id | MGI:7661172 | Doi | 10.1038/s41593-023-01415-3 |
| Citation | Jorfi M, et al. (2023) Infiltrating CD8(+) T cells exacerbate Alzheimer's disease pathology in a 3D human neuroimmune axis model. Nat Neurosci 26(9):1489-1504 |
| abstractText | 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(+) 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-gamma 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. |
