Abstract
ObjectiveTh17 has been shown to have a pivotal role in the development of arthritis. However, the role of IL-17 in the T cell-independent effector phase has not fully been examined. We investigated whether IL-17 is involved in the effector phase of arthritis by using K/BxN serum-induced arthritis model.MethodsK/BxN serum was transferred into IL-17 knockout (KO) mice, SCID mice and their control mice, and arthritis was evaluated over time. In order to clarify the source of IL-17 in the effector phase, neutrophils or CD4+ T cells collected from IL-17 KO or control mice were injected into IL-17 KO recipient mice together with K/BxN serum. To examine if neutrophils secrete IL-17 upon stimulation, neutrophils were stimulated with immune complex in vitro and IL-17 in the supernatant was measured by ELISA.ResultsK/BxN serum-induced arthritis was much less severe in IL-17 KO mice than in WT mice. Since K/BxN serum-transferred SCID mice developed severe arthritis with high serum IL-17 concentration, we speculated neutrophils are the responsible player as an IL-17 source. When wild type (WT) but not IL-17 KO neutrophils were co-injected with K/BxN serum into IL-17 KO mice, arthritis was exacerbated, whereas co-injection of WT CD4+ T cells had no effect. In vitro, stimulation of neutrophils with immune complexcaused IL-17 secretion.ConclusionsNeutrophils are essential as a source of IL-17 in the effector phase of arthritis. The trigger of secreting IL-17 from neutrophils may be immune complex.
Highlights
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovitis leading to destruction of articular cartilage and bone
We tested whether IL-17 is involved in K/BxN serum-induced arthritis using IL-17 knock out (KO) mice and we found that IL-17 derived from neutrophils affects arthritis severity in the effector phase
IL-17 Exacerbates K/BxN Serum-induced Arthritis To clarify whether IL-17 has any roles in the effector phase of arthritis, we induced K/BxN serum-induced arthritis in IL-17 KO and wild type (WT) B6 mice
Summary
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovitis leading to destruction of articular cartilage and bone. The pathophysiology of RA is still unclear, but recently the important role of IL-17-producing T cells (Th17) has been highlighted in arthritis development in human and several mouse models. IL-17 (especially IL-17A) is a proinflammatory cytokine that is thought to contribute to the inflammation, cartilage destruction and bone erosion in RA. IL-17 induces fibroblasts, endothelial cells or macrophages to secrete IL6, TNFa and IL-1 [2,3,4]. The critical role of IL-17 has been clearly demonstrated. Spontaneous development of destructive arthritis in mice deficient in IL-1 receptor antagonist was completely abrogated in the absence of IL-17 [5]. Collageninduced arthritis [3] was apparently suppressed in IL-17 knock out (KO) mice and was prevented by anti-IL-17 antibody treatment [6]
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