Inflammatory Bowel Disease

Panel A Study design. Cyclosporine A was administered at the beginning of the DSS challenge.

Panel B Administration of cyclosporine A significantly decreased body weight loss compared to 3% DSS.

Panel C Cyclosporine A treatment significantly ameliorated disease activity index (DAI) compared to 3% DSS.

Panel D Cyclosporine A treatment significantly alleviated mRNA expression level of IL-1β and IL-17A in colon compared to 3% DSS.

Panel E Cyclosporine A treatment significantly inhibited colon length shortening compared to 3% DSS.

Panel F Representative images of H&E staining slides of the colon.

3% DSS + Vehicle group: Part of the mucosal epithelium of the colon is detached, with moderate inflammatory cell infiltration in the mucosal layer, and moderate mixed inflammatory cell infiltration in the submucosa into the muscular layer, accompanied by mild to moderate edema. The number of intestinal glands decreased slightly and a few intestinal glands expanded slightly. Part of the intestinal wall was thickened, myoedema was observed, and the muscle cell interval was widened. Edema of the serous layer.

3% DSS + Cyclosporine A group: Colon structure is complete, mucosal epithelium is arranged neatly, mainly goblet cells; The number of intestinal glands decreased slightly, no atrophy or expansion was observed. Submucosal edema (black arrow); Intestinal wall thickness is normal, no muscular hyperplasia.

Panel G Cyclosporine A treatment significantly decreased H&E score of colon compared to 3% DSS.

Data are expressed as mean ± standard error (Mean ± SEM), n=8. Statistics performed using One-way ANOVA. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.

Panel A Study design. Cyclosporine A was administered at the beginning of the DSS challenge.

Panel B Administration of cyclosporine A showed a trend of attenuating body weight loss compared to the 3% DSS.

Panel C Cyclosporine A treatment significantly ameliorated disease activity index (DAI) compared to 3% DSS.

Panel D Representative images of H&E staining slides of the colon. The presence of chronic inflammation (fibrosis, abnormal colonic crypt shape) is confirmed in the DSS-induced chronic colitis model. Note: mucosal layer necrosis (black arrow); ulcer foci (green arrow); neutrophils (yellow arrow); lymphocytes (blue arrow); fibrous tissue hyperplasia (orange arrow); lymphoid follicles (red arrow); colonic crypt malformation including zig-zag shape, bifurcation structure (purple arrow). First row: Bar = 500 μm; Second row: Bar = 50 μm.

Panel E Cyclosporine A treatment significantly decreased histology score of colon compared to 3% DSS.

Data are expressed as mean ± standard error (Mean ± SEM), n=4-6. Statistics performed using One-way ANOVA. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.

Panel A Study design. Tulisokibart treatment was initiated on Day -1.

Panel B Tulisokibart treatment showed no significant difference in body weight change compared to TNBS.

Panel C Administration of Tulisokibart siginificantly attenuated DAI score compared to TNBS.

Panel D Tulisokibart treatment showed no significant difference in survival rate compared to TNBS.

Panel E Representative images of H&E staining slides of the colon. Note: Mucosal necrosis (black arrow), muscular layer degeneration and necrosis (purple arrow), ulcer focus (green arrow), crypt abscess (dark blue arrow), neutrophils (bright yellow arrow), lymphocytes (blue arrow), fibrous tissue hyperplasia (orange arrow), hemorrhage (red arrow). First row: Bar = 500 μm; Second row: Bar = 100 μm.

Panel F Tulisokibart treatment significantly decreased histology score of colon compared to TNBS.

Data are expressed as mean ± standard error (Mean ± SEM), n=5-9. Statistics performed using One-way ANOVA. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.

Panel A Study design. TCT modeling was initiated on Day 0, while anti-mouse IL-23p19 treatment was initiated on Day 28.

Panel B The initial administration of anti-mouse IL-23p19 was defined as Day 0. Treatment with anti-mouse IL-23p19 markedly alleviated body weight loss relative to the TCT group.

Panel C Anti-mouse IL-23p19 treatment siginificantly attenuated DAI score compared to TCT group.

Panel D Anti-mouse IL-23p19 treatment siginificantly decreased colon weight compared to TCT group.

Data are expressed as mean ± standard error (Mean ± SEM), n=5-8. Statistics performed using One-way ANOVA. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.

Panel A Study design. Anti-mouse TL1A and anti-mouse IL-23 antibody treatment were initiated on Day -1. Anti-CD40 antibody treatment was initiated on Day 0.

Panel B High dosage anti-mouse IL-23 administration significantly ameliorated body weight loss compared to anti-CD40 group.

Panel C Low dosage anti-mouse TL1A and high dosage anti-mouse IL-23 administration significantly decreased DAI score compared to anti-CD40 group.

Panel D Low dosage anti-mouse TL1A administration significantly mitigated histology score of colon compared to anti-CD40 group.

Data are expressed as mean ± standard error (Mean ± SEM), n=5-8. Statistics performed using One-way ANOVA. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.

Panel A Study design. HSC-NCG-M/hIL15 mice were used at 12–14 weeks post human HSC reconstitution. DSS modeling and Adalimumab treatment were initiated on Day 0.

Panel B Adalimumab administration significantly decreased DAI score compared to 3% DSS.

Panel C Adalimumab administration showed a trend of attenuating colon length shortening compared to 3% DSS.

Panel D Adalimumab administration showed a trend of attenuating mortality compared to 3% DSS.

Panel E Representative images of H&E staining slides of the colon. Note: Thickening of mucosal layer (yellow arrow); Ulcer focus (black arrow); Neutrophils (green arrow); Fibrous tissue hyperplasia (blue arrow). First row: Bar=250 μm; Second row: Bar=50 μm

Panel F Adalimumab administration significantly ameliorated the colon histology score compared to 3% DSS.

Data are expressed as mean ± standard error (Mean ± SEM), n=4-8. Statistics performed using One-way ANOVA. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.