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 γδ 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)(+) γδ 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 γδ 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 γδ T cells.