Fig. 6: Loss of IL-17RA signaling on Paneth cells results in reduced expression of Adam17 after irradiation. | Nature Communications

Fig. 6: Loss of IL-17RA signaling on Paneth cells results in reduced expression of Adam17 after irradiation.

From: IL-17RA signaling promotes the dedifferentiation of Paneth progenitors through ADAM17 to regenerate gut epithelium post-irradiation

Fig. 6: Loss of IL-17RA signaling on Paneth cells results in reduced expression of Adam17 after irradiation.The alternative text for this image may have been generated using AI.

A Gene expression from irradiated Il17rafl/fl;Defa6-cre + /− mice (6.7, 8.1 weeks old); each point represents an independent mouse. B Experimental schematic. C Adam17 expression in sorted irradiated Paneth cells after 4 h of IL-17A treatment from Defa6-cre;mT/mG organoids. N = 6. D Gene expression from irradiated Il17rafl/fl;Defa6-cre + /− mice (6.7, 8.1 weeks old). N = 13. E Single-cell RNA sequencing of Hif1a related genes from non-irradiated and irradiated Paneth cells (PMID: 29887318). F Terminal ileal Nox1 expression from irradiated Il17rafl/fl;Defa6-cre + /− mice (6.7 < 8.1 weeks old). N = 15. G Nox1 expression in sorted irradiated Paneth cells after 4 hours of IL-17A treatment. N = 5. H Single-cell RNA sequencing expression of Adam17 related genes from non irradiated and irradiated Paneth cells (PMID: 29887318). I ADAM17 activity +/- 4 mM H2O2. J Experimental schematic. K Ileum of irradiated Defa6-cre;mT/mG mice given water or 4% NAC water (GFP = green) (DAPI = blue) (scale bar = 50 μm). GFP + clones = 4 cells in a row. Mice were 8.3 and 13.4 weeks old. N = 9. L Experimental schematic. M Hematoxylin and eosin staining of terminal ilea in Il17rafl/fl;Defa6-cre + mice treated with Ad-Y5 or Ad-Adam17 (AdAD17) 5 days after irradiation (scale bar = 100 μm). Mice were 8.9, 14.1 and 15.1 weeks old. N = 11. N Ileum of Il17rafl/fl;Defa6-cre + mice treated with Ad-Y5 or AdAD17 5 days after irradiation (PCNA = green) (DAPI = blue) (scale bar = 50 μm). Mice were 8.9, 14.1 and 15.1 weeks old. N = 9. O Bacterial dissemination in Il17rafl/fl;Defa6-cre + /− mice treated with Ad-Y5 or AdAD17 5 days after irradiation. Mice were 8.9, 14.1 and 15.1 weeks old. N = 14. P EREG in the ileum of Il17rafl/fl;Defa6-cre + /− mice treated with Ad-Y5 or AdAD17 5 days after irradiation. Mice were 8.9, 14.1 and 15.1 weeks old. N = 20. N = number of biologically independent mice. 6 K, 6 M, 6 N, 6 O = 2 independent experiments. 6 A, 6 C, 6D, 6 F, 6 G, 6 L = 3 independent experiments. Outliers removed via GraphPad Prism (ROUT analysis, Q = 1%) in Fig. 6A. Data are presented as ± SEM on relevant graphs (Mann-Whitney test, Two-tailed and Wilcox paired test, Two-tailed).

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