Title | Antigen-presenting innate lymphoid cells orchestrate neuroinflammation. |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | Grigg JB, Shanmugavadivu A, Regen T, Parkhurst CN, Ahmed A, Joseph AM, Mazzucco M, Gronke K, Diefenbach A, Eberl G, Vartanian T, Waisman A, Sonnenberg GF |
Journal | Nature |
Volume | 600 |
Issue | 7890 |
Pagination | 707-712 |
Date Published | 2021 Dec |
ISSN | 1476-4687 |
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 |
Alternate Journal | Nature |
PubMed ID | 34853467 |
PubMed Central ID | PMC8702489 |
Grant List | F31 AI138389 / AI / NIAID NIH HHS / United States T32 DK116970 / DK / NIDDK NIH HHS / United States R01 AI162936 / AI / NIAID NIH HHS / United States R21 CA249274 / CA / NCI NIH HHS / United States R01 AI145989 / AI / NIAID NIH HHS / United States R01 AI123368 / AI / NIAID NIH HHS / United States R01 AI143842 / AI / NIAID NIH HHS / United States U01 AI095608 / AI / NIAID NIH HHS / United States |