Antigen-presenting innate lymphoid cells orchestrate neuroinflammation.
| Publication Type | Academic Article |
| Authors | Grigg J, Shanmugavadivu A, Regen T, Parkhurst C, Ahmed A, Joseph A, Mazzucco M, Gronke K, Diefenbach A, Eberl G, Vartanian T, Waisman A, Sonnenberg G |
| Journal | Nature |
| Volume | 600 |
| Issue | 7890 |
| Pagination | 707-712 |
| Date Published | 12/01/2021 |
| ISSN | 1476-4687 |
| Keywords | Encephalomyelitis, Autoimmune, Experimental, Multiple Sclerosis |
| Abstract | Pro-inflammatory T cells in the central nervous system (CNS) are causally associated with multiple demyelinating and neurodegenerative diseases1-6, but the pathways that control these responses remain unclear. Here we define a population of inflammatory group 3 innate lymphoid cells (ILC3s) that infiltrate the CNS in a mouse model of multiple sclerosis. These ILC3s are derived from the circulation, localize in proximity to infiltrating T cells in the CNS, function as antigen-presenting cells that restimulate myelin-specific T cells, and are increased in individuals with multiple sclerosis. Notably, antigen presentation by inflammatory ILC3s is required to promote T cell responses in the CNS and the development of multiple-sclerosis-like disease in mouse models. By contrast, conventional and tissue-resident ILC3s in the periphery do not appear to contribute to disease induction, but instead limit autoimmune T cell responses and prevent multiple-sclerosis-like disease when experimentally targeted to present myelin antigen. Collectively, our data define a population of inflammatory ILC3s that is essential for directly promoting T-cell-dependent neuroinflammation in the CNS and reveal the potential of harnessing peripheral tissue-resident ILC3s for the prevention of autoimmune disease. |
| DOI | 10.1038/s41586-021-04136-4 |
| PubMed ID | 34853467 |
| PubMed Central ID | PMC8702489 |