| First Author | McAlpine CS | Year | 2021 |
| Journal | Nature | Volume | 595 |
| Issue | 7869 | Pages | 701-706 |
| PubMed ID | 34262178 | Mgi Jnum | J:335093 |
| Mgi Id | MGI:7287758 | Doi | 10.1038/s41586-021-03734-6 |
| Citation | McAlpine CS, et al. (2021) Astrocytic interleukin-3 programs microglia and limits Alzheimer's disease. Nature 595(7869):701-706 |
| abstractText | Communication within the glial cell ecosystem is essential for neuronal and brain health(1-3). The influence of glial cells on the accumulation and clearance of beta-amyloid (Abeta) and neurofibrillary tau in the brains of individuals with Alzheimer's disease (AD) is poorly understood, despite growing awareness that these are therapeutically important interactions(4,5). Here we show, in humans and mice, that astrocyte-sourced interleukin-3 (IL-3) programs microglia to ameliorate the pathology of AD. Upon recognition of Abeta deposits, microglia increase their expression of IL-3Ralpha-the specific receptor for IL-3 (also known as CD123)-making them responsive to IL-3. Astrocytes constitutively produce IL-3, which elicits transcriptional, morphological, and functional programming of microglia to endow them with an acute immune response program, enhanced motility, and the capacity to cluster and clear aggregates of Abeta and tau. These changes restrict AD pathology and cognitive decline. Our findings identify IL-3 as a key mediator of astrocyte-microglia cross-talk and a node for therapeutic intervention in AD. |
