Fig. 2. Zonulin upregulation, decrease in tight junction proteins and barrier dysfunction before onset of arthritis.

a Time course of serum zonulin levels in mice induced for collagen-induced arthritis (CIA) (n = 5). b–d Time course of intestinal permeability assessed by b the serum FITC-Dextran, c lactulose/mannitol urine recovery ratio and d urine sucralose recovery ratio in mice induced for CIA (n = 5). e, f Quantification of ZO-1 (red) expression determined in histological sections of e the ileum (n = 6) and f the colon (n = 6) presented as floating bars (min to max) with line at median. g Representative microphotographs of ZO-1 (red) expression in small intestine. Size bar: 50 µm. h, i Quantification of occludin expression (red) in histological sections of h the ileum (n = 6) and i the colon (n = 6) presented as floating bars (min to max) with line at median with j representative microphotographs of occludin (red) expression in small intestine. Size bar: 50 µm. k, l Time course of the length measurement of k the small intestine and l the colon in mice induced for CIA. m–o Time course of m duodenal, n jejunal and o ileal crypt elongation with p representative H&E-stained sections from the ileum. Size bar: 200 µm. q Time course of goblet cell numbers in the colon and r representative PAS-stained sections from the colon. Size bar: 200 µm. Data are derived from two (b–j), three (a), or four independent (k–r) experiments and expressed as the mean ± s.d. Statistical difference was determined by one-way ANOVA. *p < 0.05; **p < 0.01; ***p < 0.001. Dashed red line: time point of clinical disease onset. Source data are provided as a Source Data file.