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 ) 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 mice were bred as homozygotes to obtain IL-23R (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.