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.