Small molecule allosteric inhibitors of RORγt block Th17-dependent inflammation and associated gene expression in vivo
Fig 7
RORγt inhibitor protects in EAE immunization model.
C57BL/6 mice were immunized with MOG35-55 peptide on day 1 and were treated orally, twice daily (from day 1-day 28) with vehicle (0.5% MC/0.25% Tween80) or RORγt inhibitors at indicated doses. FTY720 (Gilenya) was dosed once daily at 3 mg/kg starting at day 1 in MilliQ water. The clinical score (0–5) was determined in these mice from day 7–28. Scores were calculated as follows: 0- no clinical signs, 0.5- partial tail weakness, 1.0- complete tail paralysis, 1.5- flaccid tail & abnormal gait, 2.0- flaccid tail and clear weakness of hind legs, 2.5- partial paralysis in one hind limb, 3.0- complete paralysis in both hindlimbs, 4.0- partial weakness in forelimbs, 5.0- complete paralysis in both forelimbs and hindlimbs). Data are presented as mean ± SEM. Statistical significance of clinical scores were calculated by Wilcoxon’s non-parametric or 2-tailed Student’s t-test, respectively; *p < 0.05, compared with vehicle-treated EAE mice. Data are from a single experiment with n = 12/group.