Fig 2: Ependymal cell-specific inhibition of IL-17A signaling upregulates neurotrophic factors in the injured spinal cord.a Experimental time course of tamoxifen administration and RNA extraction. b Relative mRNA expression of neurotrophic factors in control (Cre-) or IL-17RA-deficient (Cre+) mice spinal cords at 2, 4, and 6 weeks after spinal cord injury (SCI) was measured on real-time polymerase chain reaction. Cre+ mice had significantly higher expression of neurotrophic factors than Cre- mice (n = 4 mice per time point, *p < 0.05, **p < 0.01, Student’s t test). Data are presented as mean ± SEM. c Diagram of the hypothesized mechanism. IL-17A, whose expression level increases in the injured spinal cord, suppresses the proliferation of ependymal cells after SCI. Ependymal cell-specific knockout of IL-17RA promotes ependymal cell proliferation, resulting in increased expression of ependymal cell-derived neurotrophic factors. Then, the reorganization of axons is promoted, resulting in functional recovery.

Fig 3: Positive and negative expression of IL17/IL17R immunohistochemistry in tissue microarray sections. (A) Positive and (B) negative expression of IL17. (C) Positive and (D) negative expression of IL17R. Original magnification, ×20. IL, interleukin; R, receptor.

Fig 4: Parietal cells express IL-17A receptor. (A) Representative immunofluorescent staining of healthy BALB/c (2 months old) mouse gastric corpus for Hoechst (blue), VEGF-B (red), and IL-17RA (yellow). A magnification pane is outlined in white showing the expression of IL-17RA on VEGF-B–expressing parietal cells. (B) Image cytometry software was used to quantify the intensity of IL-17RA fluorescence on parietal cells using immunofluorescent images. Shown is a representative plot of VEGF-B–positive parietal cells (red) and VEGF-B–negative cells (blue) with histograms of IL-17RA staining intensity in each of these groups. Epithelial cells isolated from the gastric corpus of BALB/c mice (2 months old) were cultured in media or media supplemented with IL-17A for 24 hours. Cytospin slides were generated from control and treated glands for microscopic analysis. (C) Representative immunofluorescent staining of Cytospins generated from cultured gastric epithelial cells stained with Hoechst (blue), anti–VEGF-B (red), and TUNEL (green). (D) TUNEL+ parietal cells were quantified as a percentage of total parietal cells (PCs). Data are means ± SEM of 10 representative images prepared from 6 slides over 2 separate experiments.

Fig 5: IL-17RA, IL-17RB, and IL-17RC showed differential pattern of expression in immune cells associated to lesional skin of patients with BP. Paraffin-embedded skin biopsy specimen of blistering skin from BP patients (n = 3) were subjected to double immunofluorescence staining for IL-17RA, IL-17RB, and IL-17RC (in red), and either Tryptase, CD163, or myeloperoxidase (MPO) (in green) with Hoechst counterstain. Negative control: primary antibodies were not added. Scale bar = 10 µm.