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. Author manuscript; available in PMC: 2021 Feb 4.
Published in final edited form as: Gastroenterology. 2019 Oct 14;158(3):625–637.e13. doi: 10.1053/j.gastro.2019.10.006

Figure 2. BNZ-2 blocks the transcriptional program individually and cooperatively induced by IL15 and IL21 in tissue-resident IE-CTL.

Figure 2.

(A) Venn Diagram displaying the numbers of differentially expressed genes (DEGs) in response to 700pM IL15 or 20pM IL21. The expression of 4343 genes changed in response to IL15 (FDRIL15<0.05 and FDRIL21≥0.05, IL15 specific, pink), while 115 in response to IL21 (FDRIL15≥0.05 and a FDRIL21<0.05, IL21 specific, light grey). 486 genes are changed by both cytokines (FDRIL15<0.05 and FDRIL21<0.05, IL15/IL21 shared, dark grey). (B) Heat-map displaying changes in expression levels upon stimulation with IL15 alone (FDRIL15<0.05) or IL15+IL21 (FDRIL15<0.05 and FDRIL21<0.05) combination compared to untreated IE-CTL lines. Only DEGs in response to IL21+IL15 vs IL15 alone are dispayed: 4 distinct groups were identified based on their change in expression levels. Arrows indicate up- vs down-regulation. Numbers of DEGs in each group are indicated. (C) Volcano plot displaying DEGs in response to the combination of IL15+IL21 vs IL15. Expression levels upon stimulation with IL15 were used as a baseline. p-values are on the y-axis, log2 fold changes (log2FC) in expression upon IL21 addition (IL15+IL21 vs IL15) are on the x axis. The up-regulated genes are in red on the right side, the only downregulated gene is in blue on the left. (D) Gene Ontology (GO) enrichment analysis performed including all up-regulated genes (N=41) when IL21 is added to IL15 (red dots in B), ranked based on p-values. Corrected p-value (q-value) for enrichment of DEGs in each GO term is dispayed. (E) Density plots representing the impact of 1uM BNZ-2 (blue) on IL15 and/or IL21-induced (red) differential gene expression in IE-CTL lines. A scrambled sequence of BNZ-2 served as control peptide (CP, green). Absolute log2FC are on the x axis. Number of DEGs is in the histograms. All data (A-E) are based on gene expression levels in human IE-CTL lines as assessed by RNA-seq. FDR<0.05 was used as a cut-off to evaluate DEGs.