Fig. 5: Ligand-receptor interactions between Nageotte nodules and nearby neurons identifies osteopontin (SPP1) and CD44.

A Differentially expressed ligands per Nageotte nodule cluster and corresponding receptors expressed in nearby neurons. B RNAscope in situhybridization for SCN10A (green, Nav1.8), SPP1 (red, osteopontin), CD44 (blue), and DAPI (cyan) in a diabetic peripheral neuropathy (DPN) DRG. White outline denotes the digitally zoomed-in image of a single Nageotte nodule shown in the bottom panel. Confocal, 40X. Sample size: DPN n = 5. C Top 20 expressed cytokines in Nageotte nodules clusters, showing log10(counts per million). Data points represent individual Nageotte nodule barcodes color coded by cluster (n = 1094). D Immunohistochemistry for phosphorylated eukaryotic translation initiation factor (red, p-eIF4E) and DAPI (blue) in a non-diabetic and DPN DRG. E p-eIF4E was significantly elevated in the soma of sensory neurons in the DPN DRGs. Data points represent individual donors. Sample size: Non-diabetic n = 5, DPN n = 5. F p-eIF4E was also detected at Nageotte nodules in the DPN DRGs. Statistical tests: E: Unpaired two-sided t-test. ***p = 0.0002. C, E: Error bars = mean +/- SEM. Scale bars: B: top panel—50 μm and bottom panel—10 μm. D: 200 μm. F: 50 μm. Source data is provided as a Source Data file.