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Galectin-9 is Critical for Mucosal Adaptive Immunity through the TH17-IgA Axis

Liang, CC;Li, CS;Weng, IC;Chen, HY;Lu, HH;Huang, CC;Liu, FT;

Impairment of the intestinal mucosal immunity significantly increases the risk of acute and chronic diseases. Immunoglobulin A (IgA) plays a major role in humoral mucosal immunity to provide protection against pathogens and toxins in the gut. Here, we investigated the role of endogenous galectin-9, a tandem repeat-type -galactoside-binding protein, in intestinal mucosal immunity. By mucosal immunization of Lgals9-/-and littermate control mice, it was found that lack of galectin-9 impaired mucosal antigen-specific IgA response in the gut. Moreover, Lgals9-/-mice were more susceptible to developing watery diarrhea and more prone to death in response to high-dose cholera toxin. The results indicate the importance of galectin-9 in modulating intestinal adaptive immunity. Furthermore, bone marrow chimera mice were established and galectin-9 in hematopoietic cells was found to be critical for adaptive IgA response. In addition, immunized Lgals9-/-mice exhibited lower expression of Il17 and fewer TH17 cells in the lamina propria, implying that the TH17-IgA axis is involved in this mechanism. Taken together, these findings suggest that galectin-9 plays a role in mucosal adaptive immunity through the TH17-IgA axis. By manipulating the expression or activity of galectin-9, intestinal mucosal immune response can be altered, and may benefit the development of mucosal vaccination. Copyright 2018. Published by Elsevier Inc.