IL-3 promotes the development of experimental autoimmune encephalitis
Kerstin Renner, Sonja Hellerbrand, Fabian Hermann, Christine Riedhammer, Yvonne Talke, Gabriela Schiechl, Manuel Rodriguez Gomez, Simone Kutzi, Dagmar Halbritter, Nicole Goebel, Hilke Brühl, Robert Weissert, Matthias Mack
Kerstin Renner, Sonja Hellerbrand, Fabian Hermann, Christine Riedhammer, Yvonne Talke, Gabriela Schiechl, Manuel Rodriguez Gomez, Simone Kutzi, Dagmar Halbritter, Nicole Goebel, Hilke Brühl, Robert Weissert, Matthias Mack
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Research Article

IL-3 promotes the development of experimental autoimmune encephalitis

Abstract

Little is known about the role of IL-3 in multiple sclerosis (MS) in humans and in experimental autoimmune encephalomyelitis (EAE). Using myelin oligodendrocyte glycoprotein (MOG) peptide–induced EAE, we show that CD4+ T cells are the main source of IL-3 and that cerebral IL-3 expression correlates with the influx of T cells into the brain. Blockade of IL-3 with monoclonal antibodies, analysis of IL-3 deficient mice, and adoptive transfer of leukocytes demonstrate that IL-3 plays an important role for development of clinical symptoms of EAE, for migration of leukocytes into the brain, and for cerebral expression of adhesion molecules and chemokines. In contrast, injection of recombinant IL-3 exacerbates EAE symptoms and cerebral inflammation. In patients with relapsing-remitting MS (RRMS), IL-3 expression by T cells is markedly upregulated during episodes of relapse. Our data indicate that IL-3 plays an important role in EAE and may represent a new target for treatment of MS.

Authors

Kerstin Renner, Sonja Hellerbrand, Fabian Hermann, Christine Riedhammer, Yvonne Talke, Gabriela Schiechl, Manuel Rodriguez Gomez, Simone Kutzi, Dagmar Halbritter, Nicole Goebel, Hilke Brühl, Robert Weissert, Matthias Mack

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Figure 5

Reduced development of EAE in IL-3–deficient mice.

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Reduced development of EAE in IL-3–deficient mice. EAE was induced in C5...
EAE was induced in C57BL/6 WT mice (IL-3+/+, n = 22), heterozygous IL-3–deficient mice (IL-3+/–, n = 18), and homozygous IL-3–deficient mice (IL-3–/–, n = 21) by immunization with MOG peptide 35-55 on day 0. (A) Clinical symptoms of EAE (EAE score) were significantly diminished in IL-3+/– and IL-3–/– mice, as seen by daily monitoring and by added scores (AUC). Pooled data of 2 independent experiments are shown. (B) Leukocytes were quantified in the brain and in the peripheral blood by flow cytometry on day 20 (n = 8–10/group). (C) On day 20, splenocytes were restimulated with MOG peptide 35-55 or PBS for 3 days, and the release of IL-3, GM-CSF, and IL-17 was measured in the supernatant by ELISA. Data are represented as mean ±SEM, one-way ANOVA test of IL-3+/– or IL-3–/– vs. IL-3+/+: *P ≤ 0.05, **P < 0.01, ***P < 0.001.