Antigen presenting group 3 innate lymphoid cells control neuroinflammation

Abstract

Abstract Pro-inflammatory T cells in the central nervous system (CNS) are causally associated with multiple demyelinating and neurodegenerative diseases, but the pathways controlling these responses remain unclear. Here we define a population of group 3 innate lymphoid cells (ILC3s) that are uniquely enriched in the CNS during a mouse model of multiple sclerosis. CNS-associated ILC3s exhibit distinct transcriptional profiles, localize in proximity to infiltrating T cells, and express major histocompatibility complex class II (MHCII) and co-stimulatory molecules. Critically, antigen presentation by ILC3s was required to selectively promote pro-inflammatory T cell responses in the CNS and the development of multiple sclerosis-like disease. In contrast, antigen presenting ILC3s in the periphery lack co-stimulatory molecules and did not appear to contribute to disease induction, but rather could induce tolerance in autoimmune T cells and prevent multiple sclerosis-like disease when experimentally targeted to present myelin antigen. Collectively, our data demonstrate an essential role for CNS-associated ILC3s in promoting T cell-dependent neuroinflammation and reveal the potential to harness peripheral ILC3s for the prevention of autoimmune disease.