title: Group 3 innate lymphoid cells accumulate and exhibit disease-induced activation in the meninges in EAE.
abstract: Innate lymphoid cells are immune cells that reside in tissues that interface with the external environment and contribute to the first line defense against pathogens. However, they also have roles in promoting chronic inflammation. Here we demonstrate that group 3 ILCs, (ILC3s - CD45+Lin-IL-7Rα+RORγt+), are normal residents of the meninges and exhibit disease-induced accumulation and activation in EAE. In addition to production of the pro-inflammatory cytokines IL-17 and GM-CSF, ILC3s constitutively express CD30L and OX40L, molecules required for memory T cell survival. We show that disease-induced trafficking of transferred wild type T cells to the meninges is impaired in ILC3-deficient Rorc-/- mice. Furthermore, lymphoid tissue inducer cells, a c-kit+ ILC3 subset that promotes ectopic lymphoid follicle development, a hallmark of many autoimmune diseases, are reduced in the meninges of EAE-resistant c-kit mutant Kit(W/Wv) mice. We propose that ILC3s sustain neuroinflammation by supporting T cell survival and reactivation in the meninges.
authors.affiliation: Department of Microbiology and Immunology, Driskill Graduate Program, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, United States.
authors.forename: Julianne K
authors.initials: JK
authors.lastname: Hatfield
authors.affiliation: Department of Microbiology and Immunology, Driskill Graduate Program, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, United States. Electronic address: m-brown12@northwestern.edu.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Brown
mesh_terms: D000818:Animals; D016207:Cytokines / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D005260:Female; D007113:Immunity, Innate; D007156:Immunologic Memory; D018836:Inflammation Mediators / Q000276:immunology; D016131:Lymphocyte Subsets / Q000145:classification / Q000276:immunology / Q000473:pathology; D008214:Lymphocytes / Q000145:classification / Q000276:immunology* / Q000473:pathology; D008578:Meninges / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D019009:Proto-Oncogene Proteins c-kit / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology / Q000473:pathology
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539901:Rorc protein, mouse; D019009:Proto-Oncogene Proteins c-kit
keywords: EAE; Innate lymphoid cells; MS; Meningeal inflammation; RORγt