Loss of α(1,3)‐Fucosyltransferases 4 and 7 Exacerbates DSS‐Induced Colitis

Mice deficient in α(1,3)‐fucosyltransferases 4 and 7 (FUT ‐/‐ ) lack selectin ligand activity and selectin‐dependent leukocyte trafficking. They have a granulocytosis, enhanced IL‐17 production and expanded numbers of γδ T cells. The pathogenesis of mucosal injury in colitis is thought to rely on IL‐17 and γδ T cells, and leukocyte trafficking. Therefore, we tested whether the pathogenesis of colitis is altered in FUT ‐/‐ mice. Male mice (8‐10 per group, per time point) were treated with 3% dextran sodium sulfate in drinking water for 5 days followed by 0, 3, or 5 days of untreated drinking water. Animal weight and occult rectal bleeding were monitored. At the final time point, colons were harvested, sectioned, stained, and scored for mucosal injury severity. During all three experiments, FUT ‐/‐ mice lost significantly more weight, more rapidly than WT mice. At day 10, all FUT ‐/‐ mice had died and all WT mice survived. At day 8, 80% of FUT ‐/‐ mice and all WT mice survived and colons were harvested. Colitis scores in both groups were severe (FUT ‐/‐ = 25.5 ± 2.2, WT = 22.7 ± 8.2) but not significantly different, reflecting near maximal mucosal injury in both groups. At day 5, all FUT ‐/‐ and WT mice survived. FUT ‐/‐ mice had significantly worse colitis than WT mice (colitis score of 16.0 ± 5.8 vs. 8.3 ± 3.2, respectively; p = 0.034). Thus, FUT ‐/‐ mice have worse mucosal injury in this model of colitis than WT mice. These data suggest the granulocytosis, IL‐17, and γδ T cells, alone or in combination, are primary contributors to the development of mucosal injury in this colitis model, and predominate over the potential protective effects of disrupted selectin‐dependent leukocyte trafficking. Supported by R01‐HL090823 and T32‐HL069768.