Intestinal epithelial cells express galectin-9 in patients with food allergy that plays a critical role in sustaining allergic status in mouse intestine.

Abstract

Mechanisms in sustaining the allergic hypersensitivity status in the body are unclear. Galectin-9 (Gal-9) has strong immune regulatory capacity. The present study aims to elucidate the role of Gal-9 in sustaining allergic status in the intestine. Duodenal biopsies were obtained from 20 patients with peptic ulcer and food allergy (FA). The expression of Gal-9 in intestinal tissue was examined at both protein level and mRNA level. Two coculture systems with intestinal epithelial cells (IEC) and mast cells, or dendritic cells (DC) and T cells were established to investigate the source of Gal-9 in the intestine and the mechanism by which Gal-9 modulated DC's phenotyping and sustained the T helper 2 polarization. Normal IEC showed mild expression of Gal-9 that was markedly enhanced in patients with FA. Mast cells had the capability to induce IEC to produce Gal-9 via releasing tryptase that activated the proteinase-activated receptor 2 on IEC. Gal-9 activated DC to produce TIM4 (T-cell immunoglobulin mucin domain) via ligating TIM3 on DC via activating the cyclic guanosine monophosphate (cGMP) pathway. In a mouse FA model, blocking Gal-9 inhibited the allergic hypersensitivity status and the antigen-specific Th2 response in the intestine. IEC-derived Gal-9 contributes to sustaining the allergic status in the intestine.