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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptive Immunity
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Animals
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B-Lymphocytes / immunology
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Dendritic Cells / immunology
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Dendritic Cells / metabolism
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Homeostasis
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Immunity, Innate
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Immunoglobulin A / biosynthesis
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Immunoglobulin Class Switching
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Intestinal Mucosa / immunology*
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Intestinal Mucosa / microbiology*
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Intestine, Small / immunology*
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Intestine, Small / microbiology
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Lymph Nodes / immunology
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Lymphocyte Subsets / immunology*
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Lymphocyte Subsets / metabolism
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Lymphotoxin-alpha / immunology*
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Lymphotoxin-alpha / metabolism
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Lymphotoxin-beta / immunology
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Lymphotoxin-beta / metabolism
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Mice
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Microbiota / physiology*
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Nitric Oxide Synthase Type II / genetics
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Nitric Oxide Synthase Type II / metabolism
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Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism
Substances
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Immunoglobulin A
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Lymphotoxin-alpha
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Lymphotoxin-beta
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Nuclear Receptor Subfamily 1, Group F, Member 3
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Rorc protein, mouse
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Nitric Oxide Synthase Type II
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Nos2 protein, mouse