CINCINNATI - Researchers have taken a critical step in understanding how allergic reactions occur after identifying a genetic signature for regulation of a key immune hormone, interleukin (IL-13).
Scientists from Cincinnati Children's Hospital Medical Center say the finding opens the potential for new molecular targets to treat allergic disease. They report on March 28 in Mucosal Immunology that a particular microRNA, miR-375, is regulated by IL-13, and in turns regulates how IL-13 induces pro-allergic changes, particularly in epithelial cells in the lung and esophagus.
The data support a role for miR-375 in asthma and in eosinophilic esophagitis (EoE), a severe, often painful food allergy that renders children unable to eat a wide variety of foods. EoE can also cause weight loss, vomiting, heartburn and swallowing difficulties.
"The identification of a microRNA that regulates IL-13-induced changes and inflammatory pathways is a significant advancement for the understanding and future treatment of allergic disease," says Marc E. Rothenberg, MD, senior investigator on the study and director of the Division of Allergy and Immunology and Center for Eosinophilic Disorders at Cincinnati Children's. "MiR-375 is proof of principle that microRNAs are involved in fine-tuning IL-13-mediated responses, which opens up a set of new possibilities for novel therapeutic targets for treatment of allergic disease."
IL-13 induces changes in epithelial gene and protein expression that are important in the onset of many allergic diseases, including EoE. Notably, expression of miR-375 was consistently downregulated after IL-13 stimulated human esophageal squamous and bronchial epithelial cells. Viral overexpression of miR-375 in epithelial cell cultures markedly modified the IL-13-associated immunoinflammatory pathways.
MicroRNAs are short segments of RNA that can regulate whether genetic messengers (mRNAs) are degraded or transl
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Cincinnati Children's Hospital Medical Center