Fig 2: Mutation of T779A of Il17ra and knockout of Il17rc prevent the development of skin papilloma. (A) Diagram of establishing DMBA/TPA-induced two-stage skin papilloma mouse model. (B) Representative of tumors or nodules of WT, Il17ra(T779A)-knockin, and Il17rc-knockout C57BL/6J mouse strains. Arrowheads indicate papillomata (=1mm) and nodules (<1 mm). (C–E) Plots demonstrate tumor incidence, tumor multiplicity, and tumor volume. Statistical significance was assessed with a two-tailed Student’s t test and two-way ANOVA. Error bar represents mean ± SD. *— p < 0.05; **— p < 0.01. The number of male and female mice in each subgroup are indicated in the panel.

Fig 3: Knockout of Il17rc alleviates skin lesions induced by imiquimod. (A) Diagram of establishing the imiquimod-induced psoriasis mouse model and skin lesions of WT C57BL/6J, Il17ra(T779A)-knockin, and Il17rc-knockout strains. (B) Representatives of hematoxylin and eosin stain of skin lesions. Scale bar represents 100 µm. (C) To analyze the statistical significance of the thickness of epidermis, a two-tailed Student’s t test was applied. Error bar represents mean ± SD. **** indicates p < 0.0001. The numbers of male and female mice in each group are indicated in the panel.

Fig 4: Effect of IL17RA knockdown and centrinone on squamous skin cancer cells. (A) Endogenous IL17RA of HaCaT and A431 was knocked down using small interference RNA of IL17RA. (B,C) Colony formation assay was conducted to determine the effect of IL17RA knockdown and inhibition of PLK4 on the proliferation of normal skin cell line HaCaT and squamous skin cancer cell line A431. A two-tailed Student’s t test was applied to analyze statistical significance. Error bar represents mean ± standard deviation (SD); ns—no significance; ** —p < 0.01.

Fig 5: MS patient neurons without and with exposure to inflammatory cytokines.(A) Immunofluorescence staining of iPSC-derived neurons. Mature neurons differentiated for 3 weeks stain positive for ßIII-tubulin, MAP2, IL-17RA, and TNFR1. Scale bars: 50 µm. (B) Representative images of iPSC-derived neurons treated with TNF-a/IL-17A for 24 hours (50 ng/mL). Cells were fixed and immunofluorescently stained against MAP/SMI32. Scale bars: 50 µm. (C) iPSC-derived neurons were differentiated, and monocultures of neurons were treated with cytokines for 24 hours (50 ng/mL). Immunofluorescently stained MAP/SMI32 neurons were analyzed with ImageJ and are presented as surface ratio of MAP/SMI32 ± SD, normalized to the control. In 5 of 6 neurons the ratio was increased after TNF-a/IL-17A, irrespective of their disease phenotype. (D) CRISPR/Cas9 knockout of IL-17RA in PMS1. No increase of MAP/SMI32 was detectable after TNF-a/IL-17A treatment. Each data point represents a microscopic field of view (641 × 479 µm) of 3 independent experiments depicted by different symbols; pooled data represent the mean from 3 patients and 3 independent experiments. Statistical significance was tested with a Kruskal-Wallis test; ****P < 0.0001.