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Inhibition of TGF-Beta Signaling Potential Treatment for Chronic Allergies

By BiotechDaily International staff writers
Posted on 08 Aug 2013
Image: Aberrant signaling by transforming growth factor-beta, or TGF-beta, may be responsible for disrupting the way immune cells respond to common foods and environmental allergens, leading to a wide range of allergic disorders, shows new research from Johns Hopkins (Photo courtesy of the [US] National Cancer Institute).
Image: Aberrant signaling by transforming growth factor-beta, or TGF-beta, may be responsible for disrupting the way immune cells respond to common foods and environmental allergens, leading to a wide range of allergic disorders, shows new research from Johns Hopkins (Photo courtesy of the [US] National Cancer Institute).
Mutations in the genes encoding receptor subunits for TGF-beta (transforming growth factor-beta), TGFBR1 and TGFBR2, have been linked to the development of allergic diseases, including asthma, food allergy, eczema, allergic rhinitis, and eosinophilic gastrointestinal disease.

To study the linkage between TGF-beta and allergy investigators at Johns Hopkins University (Baltimore, MD, USA) worked with a group of children aged 7 to 20 with Loeys–Dietz syndrome (LDS). Loeys–Dietz syndrome is a recently-discovered autosomal dominant genetic syndrome which has many features similar to Marfan syndrome, but which is caused by mutations in the genes encoding transforming growth factor-beta receptor 1 (TGFBR1) or 2 (TGFBR2).

The investigators reported in the July 24, 2013, issue of the journal Science Translational Medicine that patients with LDS were strongly predisposed to develop allergic diseases. The LDS patients exhibited elevated immunoglobulin E levels, eosinophil counts, and T helper 2 (TH2) cytokines in their plasma. They had an increased frequency of CD4+ T cells that expressed both Foxp3 and interleukin-13, but retained the ability to suppress effector T cell proliferation.

"Disruption in TGF-beta signaling does not simply nudge immune cells to misbehave but appears to singlehandedly unlock the very chain reaction that eventually leads to allergic disease," said senior investigator Dr. Harry C. Dietz, professor of genetic medicine at Johns Hopkins University.

Findings obtained during the course of this study highlight the potential therapeutic benefit of strategies that inhibit TGF-beta signaling in the treatment of chronic allergic disorders.

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