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IL-17-producing ©™T cells are important for the development of arthritis in a rheumatoid arthritis model
Arthritis Research & Therapy volume 14, Article number: P3 (2012)
IL-1 receptor antagonist deficient (Il1rn-/-) mice spontaneously develop arthritis. We previously demonstrated that IL-17 plays a crucial role in the development of arthritis in Il1rn-/- mice. Furthermore we showed that IL-1 Ra-deficiency in T cells is important for the development of arthritis. It is not known, however, which IL-17-producing cells are involved in the pathogenesis of arthritis in this model.
To identify the source of IL-17 in Il1rn-/- mice, we analyzed IL-17-producing cells. We found that IL-17 production from both CD4+ T cells and ©™T cells was increased in the draining lymph nodes. To clarify the roles of CD4+ T cells and ©™T cells in the development of arthritis, ©™T cells or CD4+ T cells were depleted in Il1rn-/- mice using antibodies. The development of disease was suppressed in both cases, suggesting both Th17 cells and IL-17-producing ©™T cells were involved in the pathogenesis. Then, the pathogenic role of IL-17-producing ©™T cells in the absence of Th17 cells was examined.
We generated mice with IL-17 producing ©™T cells, but without Th17 cells, by adoptively transferring Il17-/-Il1rn-/--T cells into nude mice in which IL-17-producing ©™T cells are present. We found that these mice still developed arthritis and that only ©™T cells produced IL-17. Finally, to corroborate that the development of arthritis in this transfer system is dependent on IL-17, we adoptively transferred Il17-/-Il1rn-/-- T cells into Il17-/-nu/nu mice. The development of arthritis was significantly suppressed in Il17-/-Il1rn-/-- T cell-transferred Il17-/-nu/nu mice compared with Il-17+/+nu/nu mice transferred with Il17-/-Il1rn-/-- T cells, suggesting that ©™T -cell-derived IL-17 is important for the develop arthritis.
These results indicate that ©™T cell-derived IL-17 plays an important role in the pathogenesis of arthritis in Il1rn-/- mice.