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IL-17A and IL-17F do not contribute vitally to autoimmune neuro-inflammation in mice
Stefan Haak, … , Burkhard Becher, Ari Waisman
Stefan Haak, … , Burkhard Becher, Ari Waisman
Published December 15, 2008
Citation Information: J Clin Invest. 2009;119(1):61-69. https://doi.org/10.1172/JCI35997.
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Research Article Autoimmunity

IL-17A and IL-17F do not contribute vitally to autoimmune neuro-inflammation in mice

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Abstract

The clear association of Th17 cells with autoimmune pathogenicity implicates Th17 cytokines as critical mediators of chronic autoimmune diseases such as EAE. To study the impact of IL-17A on CNS inflammation, we generated transgenic mice in which high levels of expression of IL-17A could be initiated after Cre-mediated recombination. Although ubiquitous overexpression of IL-17A led to skin inflammation and granulocytosis, T cell–specific IL-17A overexpression did not have a perceptible impact on the development and health of the mice. In the context of EAE, neither the T cell–driven overexpression of IL-17A nor its complete loss had a major impact on the development of clinical disease. Since IL-17F may be able to compensate for the loss of IL-17A, we also generated IL-17F–deficient mice. This strain was fully susceptible to EAE and displayed unaltered emergence and expansion of autoreactive T cells during disease. To eliminate potential compensatory effects of either cytokine, we treated IL-17F–deficient mice with antagonistic monoclonal antibodies specific for IL-17A and found again only a minimal beneficial impact on disease development. We conclude therefore that both IL-17A and IL-17F, while prominently expressed by an encephalitogenic T cell population, may only marginally contribute to the development of autoimmune CNS disease.

Authors

Stefan Haak, Andrew L. Croxford, Katharina Kreymborg, Frank L. Heppner, Sandrine Pouly, Burkhard Becher, Ari Waisman

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Figure 3

IL-17A is redundant in the induction of EAE, which could be due to a compensatory increase of IL-17F production.

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IL-17A is redundant in the induction of EAE, which could be due to a com...
(A) EAE was induced in Il17a–/– and Il17a+/+ mice by immunization with MOG35–55/CFA. The graph shows the development of EAE according to clinical scores (n = 10; SEM as indicated) in 1 out of 2 independent experiments. (B and C) Th17-cytokine profile measured by ELISA of splenocytes isolated from mice with active EAE and restimulated with MOG35–55 with (C) or without (B) the addition of Th17 polarizing conditions for 2 days. Error bars represent mean ± SEM. (D) Comparative mRNA expression analysis of Il17f and Il17a in the cerebellum of mice at peak EAE versus healthy controls (HC). The data represent 1 of 2 independent experiments (n = 4). (E) Th17 cells were generated in vitro from MOG35–55-immunized C57BL/6 mice. Splenocytes were harvested 7 days after immunization, Th17 polarized, and analyzed by intracellular cytokine staining for IL-17A, IL-17F, and IFN-γ. Percentages of gated cells are shown. A representative of 3 independent experiments is shown.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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