ICMI 2015

T.10 Intestinal Expression of the blood group gene b4galnt2 influences susceptibility to intestinal inflammation.

Thursday, July 16, 2015
Grand Hall and Gallery, Ground Floor & 1st Floor (Maritim Hotel)
Abdulhadi Suwandi , Institute for Experimental Medicine, Hannover, Germany
Glycans play important roles in host-microbe interactions. The glycosyltransferase gene b4galnt2 encodes a beta-1,4-N-acetylgalactosaminyltransferase known to catalyze the last step in the biosynthesis of the Sd(a) and Cad blood group antigens and is expressed in the GI tract of most mammals, including humans. Loss of B4galnt2 expression is associated with altered intestinal microbiota. We hypothesized that variation of B4galnt2 expression alters susceptibility to intestinal inflammation, induced by infection with Salmonella Typhimurium or in dextran sodium sulfate (DSS)-induced colitis.

Here, we found B4galnt2 intestinal expression was strongly associated with increased susceptibility to Salmonella as evidenced by increased histopathological changes, intestinal inflammatory cytokines and infiltrating immune cells. Fecal transfer experiments demonstrated a crucial role of the B4galnt2 dependent microbiota in conferring susceptibility to Salmonella infection. Interestingly, the loss of B4galnt2 intestinal expression increased the susceptibility to chronic DSS treatment. A significantly enhanced pathological score was found in B4galnt2 deficient mice, although lower infiltration of CD68+ and CD3+ cells were found in those mice. These data support a critical role for B4galnt2 in intestinal inflammation. We speculate that B4galnt2-specific differences in host susceptibility to intestinal inflammation underlie the strong signatures of balancing selection observed at the B4galnt2 locus in wild mouse populations.