Immunological characteristics of Tr17 cells after CII
immunization
We analyzed the expression of cell surface markers related to Treg cell
stability and function in Tr17 cells or RORγt-negative Treg cells.
Treg-specific molecules such as CD25, CTLA-4, and GITR were
significantly increased in Tr17 cells compared to
RORγt\sout--negative Treg cells both of which were
isolated from draining LNs on 10 days after 1st-CII-immunization (Figure
3a, b, c). Compared to RORγt-negative Treg cells, ICOS expression was
also upregulated in Tr17 cells, which was previously reported as a
characteristic marker molecule of Tr17 cells15(Figure
3d). Moreover, most of the Tr17 cells expressed Helios, indicating that
Tr17 cells in CIA might be differentiated from thymus-derived Treg
cells, as in a previous report on the EAE model15(Figure 3e). In Foxp3creRORγtfl/flcKO mice, although CD25 expression on Treg cells was comparable to
Foxp3wtRORγtfl/fl control mice,
CTLA-4 and GITR expression on Treg cells was significantly decreased
compared to Foxp3wtRORγtfl/flcontrol mice at 10 days after 1st CII-immunization
(Supplemental Figure 2); thus, deletion of RORγt in Treg cells results
in down-regulation of characteristic Treg cell molecules. These results
suggested that Tr17 cells detected in the course of CIA retained a Treg
cell nature with characteristic features of Tr17 cells as reported in
the EAE model, and that deletion of RORγt might attenuate Treg cell
function.