Lymphoid microenvironment in the gut for immunoglobulin A and inflammation

Abstract

Signaling through lymphotoxin beta receptor (LTbetaR) initiates the unfolding of a host of developmental programs ranging from the organogenesis of lymph nodes and Peyer's patches (PPs) to the coordination of splenic microarchitecture. While investigating an alternative pathway to immunoglobulin A (IgA) production, it was uncovered that LTbetaR signaling in the lamina propria (LP) stroma orchestrates the coordinated expression of key chemokines and adhesion molecules, creation of a cytokine milieu, and stroma development that facilitates robust IgA production independent of secondary lymphoid structures. Simultaneously, this same infrastructure can be commandeered by autoreactive T cells to organize both the acute destruction of the intestinal mucosa and chronic intestinal inflammation via the ligands for LTbetaR. The ability to modulate LTbetaR signaling may alternatively permit the suppression of autoimmune responses and augmentation of gut defenses.