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 1

MOG-specific expression of IL-3 by CD4+ T cells.

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MOG-specific expression of IL-3 by CD4+ T cells. C57BL/6 (H-2b) mice wer...
C57BL/6 (H-2b) mice were immunized with MOG peptide 35-55 on day 0. (A) Immediately before immunization (day 0) or 14 and 21 days after immunization (4–5 mice/time point), splenocytes were restimulated with MOG peptide 35-55 or PBS as control for 3 days, and the levels of IL-3, GM-CSF, and IFN-γ were measured in the supernatant. A pronounced MOG peptide 35-55–specific release of IL-3, GM-CSF, and IFN-γ was detectable 14 and 21 days after immunization. (B) Splenocytes obtained at day 14 after immunization were depleted of CD4+ or CD8+ T cells and restimulated with MOG peptide or PBS (3 mice/group). The MOG-specific release of IL-3 and GM-CSF was completely dependent on the presence of CD4+ T cells. (C) Before immunization (day 0) or 14 and 21 days after immunization, splenocytes were activated with PMA and ionomycin for 4 hours and stained for intracellular expression of IL-3, GM-CSF, IFN-γ, and IL-17 (5 mice/time point). The frequency of cytokine-positive CD4+ T cells markedly increased after immunization. One out of 2 representative experiments is shown. Data are represented as mean ±SEM, one-way ANOVA test of day 14 or day 21 vs. day 0: *P ≤ 0.05, **P ≤ 0.01, ***P < 0.001.