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. 2014 Feb 3;111(8):3074–3079. doi: 10.1073/pnas.1315792111

Fig. 4.

Fig. 4.

Gene expression in colonic ECs and responses to acute inflammation are shaped by both passive and active sources of SIgA. Seventy-day-old Pigr+/− and Pigr−/− offspring of Pigr+/− and Pigr−/− dams were left untreated or given 2% DSS in drinking water for 8 d. Global gene expression was quantified by microarray analysis of RNA from colonic ECs. RNA was collected from six mice in each treatment category, then was pooled into two samples from three mice per sample. The statistical analyses of the microarray data are described in detail in SI Appendix, Fig. S7. (A) Total number of genes significantly altered by each effect or combination (P < 0.01). (B) Relative changes in expression levels for the 1,130 differentially regulated genes described in A. (Left) Specific effects of early exposure to passive SIgA in breast milk were calculated by comparing gene expression in Pigr+/− offspring of Pigr+/− vs. Pigr−/− dams in the absence of DSS. (Center) Specific effects of endogenous, actively transported SIgA were calculated by comparing gene expression in Pigr+/− vs. Pigr−/− offspring of Pigr+/− dams in the absence of DSS. (Right) Specific effects of DSS were calculated by comparing gene expression in Pigr+/− offspring of Pigr+/− dams in the presence or absence of DSS. Dots above the red dashed line represent genes that were significantly altered by the indicated factor (P < 0.01). (C) Selected genes regulated by SIgA in mouse colonic ECs that are orthologous to human gene loci associated with CD, UC, both CD and UC (IBD), early-onset IBD, and CelD. SI Appendix, Table S2 provides a complete list of disease-associated genes that were regulated by passive SIgA, active SIgA, and DSS. (D) Multifactorial PCA was conducted using expression levels of the 1,130 differentially regulated genes described in A. Each sample represents pooled RNA from three mice, for a total of six mice per treatment group. Data for mRNA transcript levels from each sample were reduced to two PCs (PC1 and PC2). Scores were calculated as described in SI Appendix, Table S4. The points within the green oval represent the unique pattern of gene expression in mice that received both passive and active SIgA. (E) Colon pathology scores were determined for individual mice (six mice per group), and the average for each group was plotted against the average PC1 and PC2 scores from D.