Figure 5.

PAD-driven SI enteropathy is associated with defects in CD1d-mediated regulation of homeostatic iNKT cell responses in the small intestine. (A) Representative H&E images (20X magnification) of distal ileal sections from PAD mouse models are shown. (B) Radial plots are provided to show similarity between genders in each disease parameter. Cumulative enteropathy scores are compared between males and females. Student’s t-test, ns=p>0.05. (C) The severity of small bowel enteropathy among mouse strains is shown (upper plot). Dunnett’s Test (“all vs. WT”), **=p<0.01, ***=p<0.001. A regression analysis of relationship between immune dysregulation and disease severity is shown. ANOVA. (D) An MDS plot reflecting divergence among individuals based on their cumulative immunophenotypes is shown (left) and the relative effects of cumulative innate immune responses, adaptive immune responses, or IEC/ISC antigen presentation in driving immune dysregulation are compared (right). Kruskal-Wallis test, ***=p<0.001, ****=p<0.0001. (E) Results of predictive screening analysis of immune phenotypes that best predict IDI and disease severity scores among mouse strains are shown. The top 20 significant discriminators for each outcome (IDI or disease) are plotted with overlapping cellular phenotypes highlighted by connecting lines. “Contribution” reflects the contribution of each variable to variance among mouse strains in IDI or disease severity. (F) Stacked barplots showing the absolute abundance of antigen presenting phenotypes in IEC/ISC subsets are shown. (G) The absolute abundance of single positive cells (CD1d⁺MHCII^- or CD1d^-MHCII⁺) among the four IEC/ISC subsets is shown. Dunnett’s Test or Tukey’s test (“all vs. WT”), ns=p>0.05, *=p<0.05, **=p<0.01, ***=p<0.001, ****=p<0.0001. (H) A correlation matrix summarizing results of multiple linear regression analysis of relationships between IEC/ISC antigen presentation phenotypes and T cell/iNKT cell subsets identified in (E) is shown.