Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Lack of IL-17RA Signaling Prevents Autoimmune Inflammation of the Joint and Give Rise to a Th2-Like Phenotype in Collagen-Induced Arthritis.

Mus,  Anne-Marie, Corneth,  Odilia, Asmawidjaja,  Patrick, Lubberts,  Erik, MC,  Erasmus

Introduction:

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 signaling is in the development of autoimmune collagen-induced arthritis.

Objective:

To examine the role of the IL-17RA signaling in the development of CIA.

Methods:

Since the IL-17RA deficient (IL-17RA-/-) mice can not signal for IL-17A and IL-17F these mice were used in this study and were compared to control mice and the CIA resistant IL-23p19 deficient (IL-23p19-/-) mice. All mice were immunized intra-dermally with chicken type II collagen (CII) in CFA at days 0 and 21. The arthritis incidence and severity were scored macroscopically. In a set of experiments, mice were given a third CII/CFA injection at day 50. At days 20, 34, and 69 sera was collected for CII-specific IgG's measurements by ELISA. In addititon, at days 10 and 69, splenic CD4+ T cells were isolated and intracellular flow cytometry of different cytokines was performed.

Results:

CII-immunized control mice developed CIA from day 24 onwards with an incidence between 40–60%. 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-gamma+ CD4+ T cells between all three groups. Interestingly and in contrast to the IL-23p19 knockout mice, the IL-17RA deficient 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.

Discussion:

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 immunized with CII, suggesting that IL-17 receptor signaling is involved in the suppression of Th2 cytokines in autoimmune collagen arthritis.

To cite this abstract, please use the following information:
Mus, Anne-Marie, Corneth, Odilia, Asmawidjaja, Patrick, Lubberts, Erik, MC, Erasmus; Lack of IL-17RA Signaling Prevents Autoimmune Inflammation of the Joint and Give Rise to a Th2-Like Phenotype in Collagen-Induced Arthritis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1525
DOI: 10.1002/art.29291

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