L-fucose reduces gut inflammation due to T-regulatory response in Muc2 null mice

Fucose, the terminal glycan of the intestinal glycoprotein Mucin2, was shown to have an
anti-inflammatory effect in mouse colitis models and modulate immune response due to
macrophage polarization changes. In this study we evaluated the effect of 0.05% L-fucose
supplementation of drinking water on immune parameters in the intestine of homozygous mutant
Muc2 −/− , compared to Muc2 +/+   mice. To get into innate and adaptive immunity mechanisms of
gut inflammation, we tested Prkdc SCID Muc2 −/−   strain, Muc2 knockout on SCID background, that
is characterized by lack of lymphocytes, in comparison with Prkdc SCID mice. We evaluated
intestinal cytokine profiling, macrophage and eosinophil infiltration, and expression of Nos2 and
Arg1 markers of macrophage activation in all strains. Markers of Th1, Treg and Th17 cells
(Tbx21, Foxp3, and Rorc expression) were evaluated in Muc2 −/−   and Muc2 +/+   mice.
Both Muc2 −/−   and Prkdc SCID Muc2 −/−   mice demonstrated increased numbers of
macrophages, eosinophils, elevated levels of TNFa, GM-CSF, and IL-10 cytokines. In Muc2 −/−  
mice we observed a wide range of pro-inflammatory cytokines elevated, such as IFN-gamma,
IL-1b, IL-12p70, IL-6, M-CSF, G-CSF, IL-17, MCP-1, RANTES, MIP1b, MIP2. Muc2 −/−   mice
demonstrated increase of Nos2, Tbx21 and Foxp3 genes mRNA, while in Prkdc SCID Muc2 −/−   mice
Arg1 expression was increased. We found that in Muc2 −/−  mice L-fucose reduced macrophage
infiltration and IL-1a, TNFa, IFNgamma, IL-6, MCP-1, RANTES, MIP1b levels, decreased
Nos2 expression, and induced the expression of Treg marker Foxp3 gene. On the contrary, in
Prkdc SCID Muc2 −/−   mice L-fucose had no effect on macrophage and eosinophil numbers, but
increased TNFa, GM-CSF, IL-12p70, IL-6, IL-15, IL-10, MCP1, G-CSF, IL-3 levels and Nos2
gene expression, and decreased Arg1 gene expression.
We demonstrated that anti-inflammatory effect of L-fucose observed in Muc2 −/−   mice is
not reproduced in Prkdc SCID Muc2 −/− , which lack lymphocytes. We conclude that activation of
Treg cells is a key event that leads to resolution of inflammation upon L-fucose supplementation
in Muc2 −/−   mice.