Figure 6: Colitis induced by T-bet-deficient T cells is dependent on IL-23, IL-17A and IL-22.
From: T-bet is a key modulator of IL-23-driven pathogenic CD4+ T cell responses in the intestine
C57BL/6 Rag1−/− mice or Il23a−/−Rag1−/− were injected i.p. with 4 × 105 CD4+CD25-CD45RBhi T cells from C57BL/6 WT or Tbx21−/− donors. Rag1−/− recipients received weekly injections of blocking anti-IL-17A, anti-IL-22 or isotype control mAbs. Mice were killed when recipients of isotype control antibody developed clinical signs of disease (4–6 weeks). (a) Representative photomicrographs of proximal colon sections from the indicated experimental groups (× 10 magnification; scale bars, 200 μM). (b) Colitis score. (c) Primary epithelial cells were isolated from the colon of steady state C57BL/6 Rag1−/− mice and stimulated with supernatant of IL-23-stimulated WT or Tbx21−/− CD4+ T cells sort-purified from Rag1−/− recipients. Supernatants were added at 20% of total cell culture volume in combination with indicated blocking antibodies. Cells were harvested after 4 h and mRNA levels of indicated genes were analysed by quantitative reverse transcription PCR (qRT-PCR). Data in b represents pooled results from two independent experiments. Bars are the mean and each point represents an individual mouse. Data in c are pooled results from four independent experiments, bars are the mean and error bars represent s.e.m. *P<0.05, **P<0.01, ***P<0.001 as calculated by Kruskal–Wallis one-way ANOVA with Dunn’s post-test.
