Fig. 6.

Proposed model of autoimmune processes revealed by IA-predictive multi-omics signature. High ROS levels of IA-developing individuals may induce early upregulation of TNFα, leading to increased activity of APC and the activation of Th cells through FOXO1 pathway. Low levels of TGFβ and IL10 may indicate inability to control T cell proliferation, with high MMP9 suggesting an environment favorable to cell migration. This may result into inflammation, cytokinesis, and migration of immune (CD8+ T or NK) cells to the pancreatic islet, which may provoke apoptosis activation through PRF1/GZMB/Casp3 pathway. Refer to Fig. 5 for more meanings of used symbols. Heatmaps represent either gene expression levels (dark blue boxes) or pathway enrichment data (light blue boxes). From left to right, 5 time points (12, 9, 6, 3, and 0 months before seroconversion) are represented. Blue indicates downregulation and red indicates upregulation in cases