Modulation of Exaggerated-IgE Allergic Responses by Gene Transfer-mediated Antagonism of IL-13 and IL-17e.
Student Authors
Allison M. KeelerDocument Type
Journal ArticlePublication Date
2010-03-24Keywords
Immunoglobulin E; Hypersensitivity, Immediate; Interleukin-13; Interleukin-17; Receptors, IgEAllergy and Immunology
Genetics and Genomics
Immunology and Infectious Disease
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
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 reduce IgE levels probably by directly affecting B-cell maturation. These studies demonstrate the feasibility of targeting T helper 2 (Th2) cytokines with rAAV-delivered fusion proteins as a means to treat aberrant immune responses.Source
Mol Ther. 2010 Mar;18(3):511-8. Epub 2009 Nov 24. Link to article on publisher's websiteDOI
10.1038/mt.2009.264Permanent Link to this Item
http://hdl.handle.net/20.500.14038/33091PubMed ID
19935781Notes
Medical student Timothy Menz participated in this study as part of the Senior Scholars research program at the University of Massachusetts Medical School.Related Resources
Link to article in PubMedae974a485f413a2113503eed53cd6c53
10.1038/mt.2009.264