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Nonredundant function of soluble LTα3 produced by innate lymphoid cells in intestinal homeostasis


Kruglov, Andrey A; Grivennikov, Sergei I; Kuprash, Dmitry V; Winsauer, Caroline; Prepens, Sandra; Seleznik, Gitta Maria; Eberl, Gerard; Littman, Dan R; Heikenwalder, Mathias; Tumanov, Alexei V; Nedospasov, Sergei A (2013). Nonredundant function of soluble LTα3 produced by innate lymphoid cells in intestinal homeostasis. Science, 342(6163):1243-1246.

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.

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Pathology and Molecular Pathology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Visceral and Transplantation Surgery
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2013
Deposited On:12 Dec 2013 10:05
Last Modified:05 Apr 2016 17:14
Publisher:American Association for the Advancement of Science
ISSN:0036-8075
Publisher DOI:https://doi.org/10.1126/science.1243364
PubMed ID:24311691

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