Fig. 4

Effects of anti-IL-23p19 treatment in the NSG-MG model. Weekly analysis of the global clinical score in NSG-MG mouse model (A) and area under the curve for the global clinical score (B). Protein analyses of Th17-related cytokines (IL-6, TGF-β1, IL-21, TGF-β3 and IL-17A) (C) and mRNA expression of GM-CSF (D) in human AChR⁺ MG thymic biopsies engrafted in NSG-MG mice. Flow cytometry analyses of CCR6⁺CCR4⁺ T cells, CCR6⁺IL-23R⁺ T cells (Th17 cell subsets) and CD25⁺CD127⁻T cells among CD4⁺ single-positive T cells (E) in engrafted human thymic biopsies. Protein analysis of IL-2 (F) in human AChR⁺ MG thymic biopsies engrafted in NSG-MG mice. mRNA expression of IFN-γ in human thymic biopsies (G). mRNA expression levels of B cell markers (AID, PODOPLANIN, CXCL13, BLIMP1 and ST6GAL1) (H) in AChR⁺ MG thymuses engrafted in NSG-MG mice. All analyses were performed at day 42 after thymic engraftment in NSG-MG mice treated for 4 weeks with saline solution (NaCl) or anti-IL-23p19 antibody. All the data are from at least 4 different experiments performed with thymic biopsies obtained from different MG patients. For each thymic biopsy, there were n > 3 mice per treatment condition. Each box represents the mean value of at least 4 experiments. Protein and mRNA analyses were performed, respectively, by ELISA and quantitative RT-PCR. mRNA expression results were normalized to GAPDH and are expressed as arbitrary unit (AU). P values were obtained using an Anova test (Graphs A, B) and Wilcoxon matched paired test (Graphs C–H). The P values are indicated as follows: δ = 0.0625; * < 0.05; ***0.0008; ****0.0001