Fig. 4: AIF-1 induces IFN response in monocytes and promotes Th17 responses. | Nature Communications

Fig. 4: AIF-1 induces IFN response in monocytes and promotes Th17 responses.

From: Type 1 interferon signature and allograft inflammatory factor-1 contribute to refractoriness to TNF inhibition in ankylosing spondylitis

Fig. 4

a Schematic of the experimental design. PBMCs from healthy donors (n = 4) were treated with AIF-1 or control (Ctl) and subjected to scRNA-seq. In addition, CD14+ monocytes were isolated from PBMCs using CD14 Microbeads and treated with AIF-1 or Ctl, followed by bulk RNA sequencing. Created in BioRender. https://BioRender.com/q70l192. b UMAP of monocytes from AIF-1-treated PBMCs, revealing 10 clusters (n = 2245). c Dot plot showing the average expression of key markers in each cluster from AIF-1-treated UMAP. d Violin plot of log-normalized expression values for SLAMF7, GBP1, IRF7, and ISG20. e Bar plots showing the proportion of each cluster in AIF-1-treated versus Ctl PBMCs, represented as the AIF-1/Ctl ratio. f Dot plot comparing the expression of IFNAR1 and IFNGR1 between AIF-1 treated monocytes and control monocytes. The accompanying table summarizes the average log2 fold change (avg_log2FC), Bonferroni-adjusted p-value (adj p-value), and expression levels (exp) in AIF-1 treated versus control cells. (Wilcoxon rank sum test, two-sided). g Heatmap showing the expression of inflammatory cytokines (e.g., IL1B, IL6, IL-23) in monocytes treated with AIF-1 versus Ctl as determined by bulk RNA sequencing. h GSEA plot of DEGs from bulk RNA-seq, highlighting monocyte-derived dendritic cells (Mo-DCs) and BDCA1+ DC markers. i Schematic overview of the experimental design. THP-1 monocytes were transfected with siRNA targeting AIF1 (siAIF1) or scrambled control siRNA via liposomal carrier-based transfection. Created in BioRender. https://BioRender.com/q70l192. j Bulk RNA-seq analysis (n = 4) comparing the expression of AIF1 and Th17-promoting cytokines (IL1B, IL6, IL23A) between control and AIF1 knockdown (KD) THP-1 cells. Statistical comparisons performed t-test and Wilcoxon test (two-sided). Exact p-values: AIF1 = 2.68e-5, IL6 = 1.37e-5, IL23A = 7.30e-5. k FACS analysis comparing the proportion of IL-17A+ and IFNγ+ populations within memory CD4+ T cells between control and siAIF1-treated conditions (n = 5, biological replicates). Statistical significance assessed by paired t-test (two-sided). Figure 4a and i created with BioRender. Source data are provided as a Source Data file.

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