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-23RGFP/+) 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-23RGFP/+ mice were bred as homozygotes to obtain IL-23RGFP/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.
|Keywords||arthritis, CCR7, IL-17, IL-23, T cells|
|Persistent URL||dx.doi.org/10.1002/eji.201948112, hdl.handle.net/1765/122199|
|Journal||European Journal of Immunology|
Razawy, W, Asmawidjaja, P, Mus, A.M.C, Salioska, N. (Nazike), Davelaar, N, Kops, N, … Lubberts, E.W. (2019). CD4+CCR6+ T cells, but not γδ T cells, are important for the IL-23R-dependent progression of antigen-induced inflammatory arthritis in mice. European Journal of Immunology. doi:10.1002/eji.201948112