| First Author | Fitzpatrick Z | Year | 2020 |
| Journal | Nature | Volume | 587 |
| Issue | 7834 | Pages | 472-476 |
| PubMed ID | 33149302 | Mgi Jnum | J:299973 |
| Mgi Id | MGI:6492427 | Doi | 10.1038/s41586-020-2886-4 |
| Citation | Fitzpatrick Z, et al. (2020) Gut-educated IgA plasma cells defend the meningeal venous sinuses. Nature 587(7834):472-476 |
| abstractText | The central nervous system has historically been viewed as an immune-privileged site, but recent data have shown that the meninges-the membranes that surround the brain and spinal cord-contain a diverse population of immune cells(1). So far, studies have focused on macrophages and T cells, but have not included a detailed analysis of meningeal humoral immunity. Here we show that, during homeostasis, the mouse and human meninges contain IgA-secreting plasma cells. These cells are positioned adjacent to dural venous sinuses: regions of slow blood flow with fenestrations that can potentially permit blood-borne pathogens to access the brain(2). Peri-sinus IgA plasma cells increased with age and following a breach of the intestinal barrier. Conversely, they were scarce in germ-free mice, but their presence was restored by gut re-colonization. B cell receptor sequencing confirmed that meningeal IgA(+) cells originated in the intestine. Specific depletion of meningeal plasma cells or IgA deficiency resulted in reduced fungal entrapment in the peri-sinus region and increased spread into the brain following intravenous challenge, showing that meningeal IgA is essential for defending the central nervous system at this vulnerable venous barrier surface. |
