Nonredundant function of soluble ltα3 produced by innate lymphoid cells in intestinal homeostasis

Andrey A. Kruglov, Sergei I. Grivennikov, Dmitry V. Kuprash, Caroline Winsauer, Sandra Prepens, Gitta Maria Seleznik, Gerard Eberl, Dan R. Littman, Mathias Heikenwalder, Alexei V. Tumanov, Sergei A. Nedospasov

Research output: Contribution to journalArticlepeer-review

161 Scopus citations

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 a (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 (LTα1β 2) 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.

Original languageEnglish (US)
Pages (from-to)1243-1246
Number of pages4
JournalScience
Volume342
Issue number6163
DOIs
StatePublished - Jan 1 2013
Externally publishedYes

ASJC Scopus subject areas

  • General

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