Fig 2: I/R increases the expression level of IL-23 in myocardial tissue, which is further increased by AD-IL-23. I/R increased levels of IL-23, and Ad-IL-23 further enhanced the high level of IL-23 induced by myocardial I/R (n=6). #P<0.05, vs. SO group; *P<0.05, vs. I/R group. SO, sham operated; I/R, ischemia/reperfusion; IL-23, interleukin 23; Ad, adenovirus.

Fig 3: Ad-IL-23 activates the JAK2-STAT3 signaling pathway. (A) Ad-IL-23 increased the expression level of P-JAK2, but not total JAK2 in myocardial tissues in infarct and risk regions (n=6). (B) Ad-IL-23 increased the expression level of P-STAT3, but not total STAT3, in myocardial tissues from infarct and risk regions (n=6). #P<0.05, vs. SO group; *P<0.05, vs. I/R group; xP<0.05, vs. Ad-IL-23+I/R group. SO, sham operated; I/R, ischemia/reperfusion; IL-23, interleukin-23; Ad, adenovirus; JAK2, Janus kinase 2; P-JAK2, phosphorylated JAK2; STAT3, signal transducer and activator of transcription 3; P-STAT3, phosphorylated STAT3.

Fig 4: Neutrophils can produce IL23A for regulating CD4+ memory T cells through caspase-8 activation. (A) The GSEA plots of chemokine production in neutrophils and T cell activation in EM CD4+ T cells for kidney versus blood. (B) The heatmap comparing the expression of inflammation and immunoregulation factors between blood and kidney neutrophils. (C) RT-qPCR analysis of bone neutrophils for genes significantly up-regulated in kidney neutrophils between Caspase8 LoxP/LoxP and Cre MRP8 Caspase8 LoxP/LoxP mice. (D) RT-qPCR analysis of human blood neutrophils detecting gene expression changes after TNFa stimulation in vitro. (E) The western blot showing protein expression of IL23A in bone neutrophils from Caspase8 LoxP/LoxP and Cre MRP8 Caspase8 LoxP/LoxP mice. (F) The western blotting showing protein expression of IL23A in human blood neutrophils between control and TNFa groups. (G) The immunofluorescence shoots showing the relationship between IL23A (pink) secreted by neutrophils (red) and CD4+ T cells (green) in the kidney microenvironment of Caspase8 LoxP/LoxP and Cre MRP8 Caspase8 LoxP/LoxP mice. Scale bar, 20 µm. *P < 0.05, **P < 0.01, ***P < 0.001.

Fig 5: Ad-IL-23 intensifies the high expression levels of IL-17A, TNF-a and IL-6 induced by myocardial I/R, which is inhibited by AG490. (A) Levels of IL-17A in myocardial tissues from infarct and risk regions (n=6). (B) Expression levels of TNF-a and IL-6 in myocardial tissues from infarct and risk regions (n=6). #P<0.05, vs. SO group; *P<0.05, vs. I/R group; xP<0.05, vs. Ad-IL-23+I/R group. SO, sham operated; I/R, ischemia/reperfusion; IL, interleukin; Ad, adenovirus; TNF-a, tumor necrosis factor-a.