Infiltration of Tr17 cells into ankle joints after onset of CIA
through high expression of CCR6
To evaluate the characteristics of Tr17 cells, we analyzed draining LN
cells harvested from C57BL/6 mice at days 10, 42, and 56 after 1st-CII
immunization, and ankle joint (AJ) cells also harvested after arthritis
development. Tr17 cells appeared in LN following CII immunization and
increased in the ankle joints compared to LN (Figure 2a, b). Next, we
wanted to investigate how Tr17 cells accumulate in inflamed joints after
the onset of CIA. A previous study reported that CC chemokine receptor 6
(CCR6) expression contributed to the recruitment of arthritogenic Th17
cells to the inflamed joints9; therefore, we examined
the expression of CCR6 in Tr17 cells. FACS analysis revealed that CCR6
expression cells was significantly up-regulated in Tr17 cells compared
to not only RORγt-negative Treg cells but also RORγt-positive Th17 cells
(Figure 2c). Interestingly, when compared to
Foxp3wtRORγtfl/fl control mice,
expression of CCR6 was significantly down-regulated in the
Foxp3-positive Treg cells but not the Foxp3-netgative T cells of
Foxp3creRORγtfl/fl cKO mice
(Supplementary Figure 1), suggesting that infiltration of Treg cells to
inflamed joints might be impaired in
Foxp3creRORγtfl/fl cKO mice. These
findings indicate that joint infiltration of Tr17 cells might contribute
to the regulation of CIA prolongation through increased expression of
CCR6.