Fig. 8: IL23 blockade attenuates the development of CPI colitis. | Nature Communications

Fig. 8: IL23 blockade attenuates the development of CPI colitis.

From: Immune checkpoint inhibitor-induced colitis is mediated by polyfunctional lymphocytes and is dependent on an IL23/IFNγ axis

Fig. 8

a Network analysis, using Enhanced Causal Network using Qiagen IPA, of predicted upstream regulators of Ifng-expressing CD4+ T cell in CPI colitis. Multiple cytokines, transmembrane receptors and transcriptional regulators were predicted to significantly (FDR < 0.05) regulate Ifng-expressing CD4+ T cell. b Representative flow cytometry plot and c percentage of IFNγ+/TNFα+ CD4+ T cells from wildtype female 6-week-old CPI colitis mice treated with an isotype control (n = 7) or an IL-23 blocking antibody (n = 8). Two-tailed Mann–Whitney Test performed where *P = 0.019. d Colon mass, in either control mice (n = 12) or wildtype female 6-week-old CPI colitis mice treated with an isotype control (n = 23) or an IL-23 blocking antibody (n = 24). Kruskal-Wallis test with Dunn’s multiple comparison used where ****P < 0.0001. e Gr-1hi neutrophil counts in either wildtype female 6-week-old CPI colitis mice treated with an isotype control (n = 24) or an IL-23 blocking antibody (n = 26), using a two-tailed Mann–Whitney Test to show ***P = 0.0006 and f Average colitis score, using the same previous colitis score parameters, in either control mice (n = 7) or wildtype female 6-week-old CPI colitis mice treated with an isotype control (n = 17) or an IL-23 blocking antibody (n = 8). Bar graph showing mean with SEM and Two-way ANOVA with Tukey’s multiple comparison test used whereby ****P < 0.0001. g Colon mass, using a two-tailed Mann–Whitney Test to show ***P = 0.0003, and h Gr-1hi neutrophil counts in either wildtype female 6-week-old mice (n = 17) or female 6-week-old Il23−/− mice (n = 20) treated with CPI colitis. A two-tailed Mann–Whitney Test to show **P = 0.005, i Percentage of IFNγ+/TNFα+ CD4+ T cells from CPI colitis treated wildtype female 6-week-old mice (n = 8) or female 6-week-old Il23−/− mice (n = 12). A two-tailed Mann–Whitney Test to show *P = 0.0, j PathLinker network analysis of Ifng-expressing CD4+ T cell in CPI colitis showing the highest-ranking shortest paths involving differentially expressed genes linking Il23r to Ifng through regulatory and protein-protein interactions queried from OmniPath. Paths with wider edges rank higher with upregulated genes shown in orange, downregulated in blue.

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