Mast cell number reduced in Tenapanor treated intestine
An increase in innate immune cells, particularly mast cells, has been shown in the small intestine of Cftr-/- mice (Norkina, Kaur, Ziemer & De Lisle, 2004). Importantly, a recent study highlighted the mast cell-dependent immune function to a worse survival in F50del mutant mice (Philp et al., 2018). We therefore studied mast cell numbers and the effect of tenapanor treatment. A significant increase of Toluidine Blue stained mast cells were seen in all examined intestinal segments of the Cftr-/- compared toCftr+/+ mice (Figure 6a, b). Treatment with tenapanor resulted in a significant reduction in the number of mast cells in the jejunum and mid-distal colon ofCftr -/- mice, which were also the segments with the highest mast cell numbers in the epithelium (outside of Peyer´s patches). In other segments, while there was a similar trend, it did not reach statistical significance. No differences in mast cell number were seen between vehicle and tenapanor treatedCftr+/+ mice groups (Figure 6a,b).