Fig. 5: The vitamin D receptor is a predicted regulator of effector Treg cell differentiation.

a Network inference of key-regulators driving peripheral blood (PB) to synovial fluid (SF) Treg cell differentiation on RNA level, based on unsupervised weighted correlation network analysis followed by Fisher’s exact test of the transcription factors and co-factors (red = upregulation, green = downregulation). The purple lines depict connections between regulators and their targets. Circle size indicates −log10(p) for each comparison, with the p(-value) derived from differential expression analysis (log fold change > 1), and the text size represents the RegEnrich score; for both, larger indicates higher scores (see also Supplementary Data 3). b The RNA expression profile of VDR from JIA SF Treg cell samples 1–4 to adult PB Treg cell samples 1–4 indicated by the yellow line, with its associated genes in gray; values are normalized to the Z-score. c All genes associated with VDR defined by the key-regulator network inference. d Pearson’s correlation plot of VDR and FOXP3 (left) and T-bet (right) Median Fluorescence Intensity (MFI’s) in PB (circles) and SF (triangles) with the line fitted by linear regression (n = 12 PB HC and PB JIA (PBMC), n = 8 SF JIA (SFMC)). e Relative expression fold change (2^ΔΔCT) of IL2RA, CTLA4, TNFRSF8, IL10, TBX21, IRF4, and VDR (lower left panel) on Treg cells upon incubation of 50,000 activated CD3⁺CD4⁺CD25⁺CD127^low sorted Treg cells from HC PB with 10 nM vitamin D compared to without vitamin D for 2 days (n = 4, mean ±  SEM). f Relative MFI changes of CD25 (IL2RA), CTLA4, and TNFRSF8 following experiment as per e with (n = 7, mean ± SEM). d–f Data are representative of two independent experiments. Source data are provided as a Source Data file.