Suppression of CIA in Foxp3creRORγtfl/fl mice
To confirm the functional role of Tr17 cells on the development of arthritis, we generated Foxp3creRORγtfl/fl mice in which the gene encoding RORγt specifically in Foxp3-expressing cells and was induced CIA in these mice. We first checked RORγt expression in Foxp3+ Treg cells after the immunization of CII in Foxp3creRORγtfl/fl mice, and compared it with Foxp3wtRORγtfl/flcontrol mice. Frequency of RORγt-expressing Foxp3+Tr17 cells was significantly decreased in Foxp3creRORγtfl/fl mice compared with Foxp3wtRORγtfl/fl mice (Figure 1a). While the incidence and severity of arthritis was almost unchanged in Foxp3creRORγtfl/fl mice compared with Foxp3wtRORγtfl/fl mice, severe arthritis was significantly prolonged in Foxp3creRORγtfl/fl mice than in Foxp3wtRORγtfl/fl mice from 56 days after 1st-CII immunization (Figure 1b, c). Joint inflammation and erosion scores tended to be increased in Foxp3creRORγtfl/fl mice compared with Foxp3wtRORγtfl/fl mice (Figure 1d). We examined serum CII-specific IgG in Foxp3creRORγtfl/fl mice using ELISA, because CII-specific IgG level is known to correlate with the development of CIA. There was no difference in CII-specific total IgG between Foxp3creRORγtfl/fl mice and Foxp3wtRORγtfl/fl mice at day 75 post first CII immunization (Figure 1e). These results proved significant prolongation of arthritis in CIA with Tr17-deficient mice, and it was not associated with anti-CII antibody.