Nonredundant Function of Soluble LTα3 Produced by Innate Lymphoid Cells in Intestinal Homeostasis

AA Kruglov, SI Grivennikov, DV Kuprash, C Winsauer… - Science, 2013 - science.org
AA Kruglov, SI Grivennikov, DV Kuprash, C Winsauer, S Prepens, GM Seleznik, G Eberl…
Science, 2013science.org
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 …
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.
AAAS