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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 2

Systemic overexpression of IL-17A in Del-IL17Aind/+ leads to granulocytosis and anemia.

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Systemic overexpression of IL-17A in Del-IL17Aind/+ leads to granulocyto...
(A) Crossing the IL-17Aind allele to the delete-cre strain yields mice called Del-IL17Aind/+. Skin inflammation, stunted growth, and failure to thrive is a consistent phenotype in all mice observed when compared with delete-cre littermate controls (Del). (B) Single-cell suspensions from bone marrow, spleen (SPL), thymus (THY), and mesenteric LNs (mLN) were placed in unstimulated culture for 24 hours, after which IL-17A secretion was assayed by ELISA. Error bars represent mean ± SEM. (C) Bone marrow cells were isolated from Del-IL17Aind/+ mice and littermate controls and surface stained for Gr1 and CD11b. Percentages of gated granulocytes are shown in quadrant corners. (D) Isolated spleen cells and PBMCs from the indicated genotypes were stained for MHC-class II and Gr1. Percentages of gated cells are shown. (A–D) Data shown are representative of at least 2 independent experiments.

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

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