Supplementary Figure 7: RIDD activity promotes survival of XBP1 deficient intestinal cDC1s.
From: Regulated IRE1-dependent mRNA decay sets the threshold for dendritic cell survival
(a) no of lung cDC2s in XBP1/IRE1 WT, XBP1ΔDC, XBP1ΔDC/IRE1WT/truncDC and XBP1ΔDC/IRE1truncDC. Bar graphs represent mean +/- S.E.M. (nXBP1/IRE1WT = 13 mice, nXBP1ΔDC = 8 mice, nXBP1ΔDC/IRE1WT/truncDC = 7 mice, nXBP1ΔDC/IRE1truncDC = 6 mice). Kruskal-Wallis test with Dunn’s multiple comparisons. (b–d) Percentage of resident cDC1s (b) resident cDC2s (c) migratory cDC2s (d) in the MedLN of XBP1/IRE1 WT, XBP1ΔDC, XBP1ΔDC/IRE1WT/truncDC and XBP1ΔDC/IRE1truncDC mice. Bar graphs represent mean percentage +/- S.E.M. (nXBP1/IRE1WT = 20 mice, nXBP1ΔDC = 14 mice, nXBP1ΔDC/IRE1WT/truncDC = 12 mice, nXBP1ΔDC/IRE1truncDC = 5 mice). Kruskal-Wallis test with Dunn’s multiple comparisons. (e) Number of intestinal cDC2s of XBP1/IRE1 WT, XBP1ΔDC, XBP1ΔDC/IRE1WT/truncDC and XBP1ΔDC/IRE1truncDC mice. Bar graphs represent mean +/- S.E.M. (nXBP1/IRE1WT = 13 mice, nXBP1ΔDC = 8 mice, nXBP1ΔDC/IRE1WT/truncDC = 7 mice, nXBP1ΔDC/IRE1truncDC = 6 mice). Kruskal-Wallis test with Dunn’s multiple comparisons. (f–h) Percentage of resident cDC1s (f), resident cDC2s (g), migratory cDC2s (h) in the MesLN of XBP1/IRE1 WT, XBP1ΔDC, XBP1ΔDC/IRE1WT/truncDC and XBP1ΔDC/IRE1truncDC mice. Bar graphs represent mean percentage +/- S.E.M. (nXBP1/IRE1WT = 16 mice, nXBP1ΔDC = 12 mice, nXBP1ΔDC/IRE1WT/truncDC = 13 mice, nXBP1ΔDC/IRE1truncDC = 11 mice). Kruskal-Wallis test with Dunn’s multiple comparisons. ∗: p < 0,05, ∗∗:p < 0,01, ∗∗∗:p < 0,005. Data are pooled across 2 independent experiments. (i) graphical scheme illustrating RIDD activation upon XBP1 deletion in cDC1s. Endonuclease activity of IRE1 was inhibited with complementary genetic (IRE1trunc) and chemical (B-I09) approaches. Inhibition of RIDD induced cell death of chronically stressed cDC1s due to XBP1 deficiency.
