Antigen-presenting innate lymphoid cells orchestrate neuroinflammation.

TitleAntigen-presenting innate lymphoid cells orchestrate neuroinflammation.
Publication TypeJournal Article
Year of Publication2021
AuthorsGrigg, 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
JournalNature
Date Published2021 Dec 01
ISSN1476-4687
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.

DOI10.1038/s41586-021-04136-4
Alternate JournalNature
PubMed ID34853467