Control of microbiota by LTa produced by RORgt+ cells. Lymphotoxin alpha and microbiota

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 (ILC) controls T-cell-dependent IgA induction in the lamina propria via regulation of T cell homing to the gut. On the other hand, membrane-bound lymphotoxin β (LTα1β2) produced by RORγt+ ILC 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 ILC distinctly organize adaptive immune responses in the gut and control commensal microbiota composition.