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Updated: Aug 16, 2026
Induction of Murine Intestinal Inflammation by Adoptive Transfer of Effector CD4+CD45RBhigh T Cells into Immunodeficient Mice
Published on: April 21, 2015
Suppressing α-1,6-Fucosyltransferase With a Novel Small Molecule Inhibitor Ameliorates Inflammation in Murine
Akiko Asakura1, Shinichiro Shinzaki2, Yoshiyuki Manabe3
1Department of Gastroenterology and Hepatology, Graduate School of Medicine, The University of Osaka, Osaka, Japan.
Background & Aims:
Inflammatory bowel disease involves intractable intestinal inflammation often refractory to current pharmacotherapies. We investigated the therapeutic potential of a novel, orally available inhibitor targeting α-1,6-fucosyltransferase-the sole glycosyltransferase catalyzing core fucosylation of N-glycans in mammals-as an anti-inflammatory agent.
Methods:
α-1,6-Fucosyltransferase inhibitor efficacy was evaluated in 2 murine models: a trinitrobenzene sulfonic acid-induced colitis model and a naive CD4+ T-cell adoptive transfer model using recombination activating gene 2 (Rag2)-deficient mice. Amelioration of trinitrobenzene sulfonic acid-induced colitis by the α-1,6-fucosyltransferase inhibitor was also evaluated in LckcreFut8fl/fl mice in which α-1,6-fucosyltransferase is conditionally abrogated in T cells. Splenic CD4+ T cells from wild-type mice were treated with the α-1,6-fucosyltransferase inhibitor to evaluate its effects on cell signaling, cytokine production, and T helper 1, 2, and 17 differentiation. In vivo safety was assessed in wild-type mice.
Results:
Oral administration of the α-1,6-fucosyltransferase inhibitor effectively decreased T-cell core fucosylation and ameliorated trinitrobenzene sulfonic acid-induced colitis and colitis induced by adoptive T-cell transfer. These clinical effects were accompanied by decreased T helper 1 and 2 cytokine production from CD4+ T cells. Trinitrobenzene sulfonic acid-induced colitis was attenuated in LckcreFut8fl/fl mice, demonstrating that the ameliorative effect of α-1,6-fucosyltransferase inhibition is directly mediated by T cells. In vitro, the inhibitor suppressed T-cell signal transduction and T helper 1, 2, and 17 cell differentiation. No apparent hepatorenal toxicity or intestinal mucus layer disruption was observed.
Conclusions:
α-1,6-Fucosyltransferase inhibition modulated T-cell core fucosylation and reduced inflammation in murine colitis models without apparent toxicity, indicating that targeting α-1,6-fucosyltransferase may offer a novel therapeutic approach for inflammatory bowel disease by disrupting proinflammatory T-cell responses.
