Goblet cell differentiation leads to reduced cytokine expression and innate immune cell infiltration.

<p>(A) Alcian Blue/Periodic Acid Schiff (AB/PAS) stain for mucin shows loss of goblet cells in inflamed animals that is restored by treatment with the Notch pathway inhibitor dibenzazepine (DBZ). (B) Immune infiltrate, as measured by flow cytometry expressed as a percentage of total cells, shows a reduction in macrophages and neutrophils following 1-week treatment with DBZ. Significance determined by unpaired <i>t</i> test, with <i>p</i>-values indicated above each cell type. <i>N</i> = 2–3 animals per condition. Bar graphs represent mean +/− standard error. (C) Inflammation-associated cytokine and chemokine expression was measured by Luminex and displayed as log2-fold changes versus control animals. These proteins represent the top 20 loadings from the partial least squares regression (PLSR) model described in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2002417#pbio.2002417.g005" target="_blank">Fig 5D</a>. Data for individual animals are presented in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2002417#pbio.2002417.s009" target="_blank">S8 Fig</a>. (D) DBZ- and vehicle (Veh.)-treated cytokine and chemokine measurements were projected onto a PLSR model built from non-drug-treated animals. DBZ-treated animals cluster with focal inflamed and noninflamed animals. Original samples used to generate the model project into the gray rectangle (control), blue rectangle (focal inflammation), and red rectangle (continuous inflammation). Underlying numerical values for panels B–D are provided in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2002417#pbio.2002417.s001" target="_blank">S1 Data</a>. Avg, average; IFNγ, interferon gamma; IL, interleukin; LIF, leukemia inhibitory factor; LV1, latent variable 1; MCP-1, monocyte chemoattractant protein 1; MIG, mitokine induced by gamma interferon; MIP-1α/β, macrophage inflammatory protein 1-alpha/beta; M-CSF, macrophage colony-stimulating factor; RANTES, regulated on activation, normal T cell expressed and secreted; VEGF, vascular endothelial growth factor.