Modulation of exaggerated-IgE allergic responses by gene transfer-mediated antagonism of IL-13 and IL-17e.

Molecular Therapy : the Journal of the American Society of Gene Therapy
Christian MuellerTerence R Flotte

Abstract

Asthma and allergic rhinitis are almost invariable accompanied by elevated levels of immunoglobin E (IgE), and more importantly a genetic link between IgE levels and airway hyper-responsiveness has been established. We hypothesized that expression of soluble receptors directed against interleukin (IL)-13 and IL-17e would prevent the cytokines from engaging the cell-bound receptors and therefore help to attenuate allergic responses in a Cftr(-/-)-dependent mouse model of exaggerated-IgE responses. Cftr(-/-) mice were injected with recombinant adeno-associated virus 1 (rAAV1) intramuscularly expressing soluble receptors to IL-17e (IL-17Rh1fc) or IL-13 (IL-13Ralpha2Fc). Total IgE levels, in mice receiving the IL-17Rh1fc and IL-13Ralpha2Fc therapy, were lower than in the control group. Interestingly Aspergillus fumigatus (Af)-specific IgE levels were undetectable in both the mice receiving the IL-17Rh1fc and IL-13Ralpha2Fc therapies. Further flow cytometry analysis of intracellular gene expression suggests that blocking IL-17e may be interfering with signaling upstream of CD4+ and CD11b+ cells and reducing IgE levels by affecting signaling on these cell populations. In contrast it appears that IL-13 blockade acts downstream to redu...Continue Reading

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Citations

Feb 22, 2012·International Journal of Nanomedicine·Chia-Hung ChenKuang-Wen Liao
Apr 27, 2012·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Kathleen R Bartemes, Hirohito Kita
Jan 15, 2016·Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine·Qiyuan TianJennifer A McNab

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