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Lack of IL-17RA signalling prevents autoimmune inflammation of the joint and give rise to a Th2-like phenotype in collagen-induced arthritis
  1. Anne-Marie Mus1,2,
  2. Odilia Corneth1,2,
  3. Patrick Asmawidjaja1,2,
  4. Erik Lubberts1,2
  1. 1Departments of Rheumatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
  2. 2Immunology, Erasmus MC University Medical Center, Rotterdam, The Netherlands; A-MM and OC equally contributed to this study

Abstract

Interleukin (IL)-17A plays an important role in collagen-induced arthritis (CIA). On the other hand, CIA developed normally in IL-17F deficient mice. This could be due to IL-17A that is still expressed in these mice. It has been shown that around 20% of the IL-17A deficient mice still develop marked collagen-induced arthritis with a somewhat lower severity that the control littermates. Spontaneous arthritis development in the IL-1Ra deficient mice could not be completely prevented in double IL-17A/IL-17F deficient mice. However, it is still not fully clear how important the role of the IL-17A and IL-17F signalling is in the development of autoimmune collagen-induced arthritis.

Here the authors examined the role of the IL-17RA signaling in the development of CIA using IL-17RA deficient (IL-17RA−/−) mice that can not signal for IL-17A and IL-17F. These mice were compared to control mice and the CIA resistant IL-23p19 deficient (IL-23p19−/−) mice.

CII-immunised control mice developed CIA from day 24 onwards with an incidence between 40% and 60%. As expected, the IL-23p19−/− mice did not develop CIA. Interestingly, the IL-17RA−/− mice were completely protected and did not develop CIA even after a third CII/CFA injection. In contrast to the low percentage of IL-17+ CD4+ T cells in the IL-23p19−/− mice, there was a significant increase in the percentage of these cells in the IL-17RA−/− group compared to the control group at day 69. No significant difference was found in the percentage of IFN-γ+ CD4+ T cells between all three groups. Interestingly and in contrast to the IL-23p19 knockout mice, the IL-17RA deficient mice showed a Th2-like phenotype in splenic CD4 T cells at day 69. No difference was noted for FoxP3 expression in the splenic CD4 T cells between the three different mouse groups. Moreover, the CII-specific IgG2a levels in the sera of IL-17RA−/− was significantly lower compared to the control group at day 20 and lower although not statistically significant at day 69. At this latter time point, CII-specific IgG1 levels in the sera of IL-17RA−/− was increased although not statistically significant compared to the control.

These data revealed a critical role for the IL-17RA signaling in the development of autoimmune inflammation of the joint. Moreover, these data show a Th2-like phenotype in IL-17RA−/− mice immunised with CII, suggesting that IL-17 receptor signaling is involved in the suppression of Th2 cytokines in autoimmune collagen arthritis.

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