| First Author | Schonhoff AM | Year | 2023 |
| Journal | Nat Commun | Volume | 14 |
| Issue | 1 | Pages | 3754 |
| PubMed ID | 37365181 | Mgi Jnum | J:337440 |
| Mgi Id | MGI:7495173 | Doi | 10.1038/s41467-023-39060-w |
| Citation | Schonhoff AM, et al. (2023) Border-associated macrophages mediate the neuroinflammatory response in an alpha-synuclein model of Parkinson disease. Nat Commun 14(1):3754 |
| abstractText | Dopaminergic cell loss due to the accumulation of alpha-syn is a core feature of the pathogenesis of Parkinson disease. Neuroinflammation specifically induced by alpha-synuclein has been shown to exacerbate neurodegeneration, yet the role of central nervous system (CNS) resident macrophages in this process remains unclear. We found that a specific subset of CNS resident macrophages, border-associated macrophages (BAMs), play an essential role in mediating alpha-synuclein related neuroinflammation due to their unique role as the antigen presenting cells necessary to initiate a CD4 T cell response whereas the loss of MHCII antigen presentation on microglia had no effect on neuroinflammation. Furthermore, alpha-synuclein expression led to an expansion in border-associated macrophage numbers and a unique damage-associated activation state. Through a combinatorial approach of single-cell RNA sequencing and depletion experiments, we found that border-associated macrophages played an essential role in immune cell recruitment, infiltration, and antigen presentation. Furthermore, border-associated macrophages were identified in post-mortem PD brain in close proximity to T cells. These results point to a role for border-associated macrophages in mediating the pathogenesis of Parkinson disease through their role in the orchestration of the alpha-synuclein-mediated neuroinflammatory response. |
