title: Nonredundant function of soluble LTα3 produced by innate lymphoid cells in intestinal homeostasis.
abstract: Immunoglobulin A (IgA) production at mucosal surfaces contributes to protection against pathogens and controls intestinal microbiota composition. However, mechanisms regulating IgA induction are not completely defined. We show that soluble lymphotoxin α (sLTα3) produced by RORγt(+) innate lymphoid cells (ILCs) controls T cell-dependent IgA induction in the lamina propria via regulation of T cell homing to the gut. By contrast, membrane-bound lymphotoxin β (LTα1β2) produced by RORγt(+) ILCs is critical for T cell-independent IgA induction in the lamina propria via control of dendritic cell functions. Ablation of LTα in RORγt(+) cells abrogated IgA production in the gut and altered microbiota composition. Thus, soluble and membrane-bound lymphotoxins produced by ILCs distinctly organize adaptive immune responses in the gut and control commensal microbiota composition.
authors: German Rheumatism Research Center (DRFZ), a Leibniz Institute, Berlin 10117, Germany.
authors: Andrey A
authors: AA
authors: Kruglov
authors: Sergei I
authors: SI
authors: Grivennikov
authors: Dmitry V
authors: DV
authors: Kuprash
authors: Caroline
authors: C
authors: Winsauer
authors: Sandra
authors: S
authors: Prepens
authors: Gitta Maria
authors: GM
authors: Seleznik
authors: Gerard
authors: G
authors: Eberl
authors: Dan R
authors: DR
authors: Littman
authors: Mathias
authors: M
authors: Heikenwalder
authors: Alexei V
authors: AV
authors: Tumanov
authors: Sergei A
authors: SA
authors: Nedospasov
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D006706:Homeostasis; D007113:Immunity, Innate; D007070:Immunoglobulin A / Q000096:biosynthesis; D017578:Immunoglobulin Class Switching; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology*; D007421:Intestine, Small / Q000276:immunology* / Q000382:microbiology; D008198:Lymph Nodes / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D008233:Lymphotoxin-alpha / Q000276:immunology* / Q000378:metabolism; D053308:Lymphotoxin-beta / Q000276:immunology / Q000378:metabolism; D051379:Mice; D064307:Microbiota / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D007070:Immunoglobulin A; D008233:Lymphotoxin-alpha; D053308:Lymphotoxin-beta; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539901:Rorc protein, mouse; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse