CD4+CCR6+ T cells, but not γδ T cells, are important for the IL-23R-dependent progression of antigen-induced inflammatory arthritis in mice

IL-23 plays an important role in the development of arthritis and the IL-23 receptor (IL-23R) is expressed on different types of T cells. However, it is not fully clear which IL-23R(+) T cells are critical in driving T cell-mediated synovitis. We demonstrate, using knock-in IL-23R-GFP reporter (IL-23R(GFP/+)) mice, that CD4(+)CCR6(+) T cells and gamma delta T cells, but not CD8(+) T cells, express the IL-23R(GFP). During early arthritis, IL-23R(GFP)(+)CD4(+)CCR6(+) T cells, but not IL-23R(GFP)(+) gamma delta T cells, were present in the inflamed joints. IL-23R(GFP/+) mice were bred as homozygotes to obtain IL-23R(GFP/GFP) (IL-23R deficient/IL-23R(-/-)) mice, which express GFP under the IL-23R promotor. Arthritis progression and joint damage were significantly milder in IL-23R(-/-) mice, which revealed less IL-17A(+) cells in their lymphoid tissues. Surprisingly, IL-23R(-/-) mice had increased numbers of IL-23R(GFP)(+)CD4(+)CCR6(+) and CCR7(+)CD4(+)CCR6(+) T cells in their spleen compared to WT, and IL-23 suppressed CCR7 expression in vitro. However, IL-23R(GFP)(+)CD4(+)CCR6(+) T cells were present in the synovium of IL-23R(-/-) mice at day 4. Finally, adoptive transfer experiments revealed that CD4(+)CCR6(+) T cells and not gamma delta T cells drive arthritis progression. These data suggest that IL-23R-dependent T cell-mediated synovitis is dependent on CD4(+)CCR6(+) T cells and not on gamma delta T cells.