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Assays for Validating Histone Acetyltransferase Inhibitors
Published on: August 6, 2020
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Targeting histone-acetyltransferase Tat-interactive protein 60 inhibits intestinal allergy
G Yang1,2, B-H Cheng1, S-B Yang3
1The Affiliated ENT Hospital and the Research Center of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China.
Allergy
|September 6, 2017
Summary
The histone acetyltransferase Tip60 is crucial for IgE production in B cells, driving allergic responses. Inhibiting Tip60 may offer a new strategy for treating food allergies.
Area of Science:
- Immunology
- Molecular Biology
- Allergy Research
Background:
- Overproduction of immunoglobulin E (IgE) is central to allergy pathogenesis, but underlying mechanisms remain unclear.
- Histone acetyltransferase (HAT) activities are essential for transcribing genes involved in immune responses.
Purpose of the Study:
- To investigate the role of HAT Tat-interactive protein 60 (Tip60) in initiating IgE-mediated allergy.
- To test the hypothesis that Tip60 is a key regulator of IgE expression and allergic inflammation.
Main Methods:
- Assessed Tip60's effects on IgE expression in B cells.
- Developed an intestinal allergy mouse model to study Tip60's role in allergic inflammation.
- Examined chromatin remodeling, histone acetylation, STAT6, and NF-κB at the Iε promoter.
Main Results:
- Elevated Tip60 levels were found in peripheral B cells of patients with food allergy (FA).
- Tip60 was essential for IgE and IgG1 expression in B cells, promoting chromatin remodeling and increasing histone acetylation, STAT6, and NF-κB.
- Blocking Tip60 significantly reduced allergic inflammation in the intestinal mucosa of mice.
Conclusions:
- Tip60 plays a significant role in inducing IgE production by B cells.
- Inhibiting Tip60 ameliorates intestinal allergic inflammation, indicating Tip60 inhibitors as potential anti-allergy therapeutics.
