Targeting histone deacetylases to restore epithelial barrier integrity: A new option for personalized medicine in patients with allergic airway disorders?

• Published in: Journal of allergy and clinical immunology Vol. 144; no. 5; pp. 1172 - 1174
• Main Author: Georas, Steve N.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2019; Elsevier Limited
• Subjects: allergic rhinitis; Asthma; barrier dysfunction; Cancer; Chromatin; Cytokines; E-cadherin; Epigenetics; epithelial cell; Epithelial cells; Epithelium; Genes; Genetic transformation; Histone deacetylase; Histone Deacetylases; Humans; Immunofluorescence; Inflammation; Lysine; Mesenchyme; mRNA; personalized medicine; Precision Medicine; Protein expression; Proteins; Respiratory System; Respiratory tract; Respiratory tract diseases; Rhinitis; Rhinitis, Allergic; Substrate specificity; tight junction; Tumors; allergic rhinitis; epithelial cell; barrier dysfunction; histone deacetylase; tight junction; epigenetics; Asthma; personalized medicine
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2019.09.007

Expression of HDAC5 and HDAC11 mRNA and protein was enhanced in cells from a few subjects, providing a potential explanation for increased HDAC activity. Because the HDAC inhibitor (called JNJ-26481585) enhanced both barrier function and junctional protein immunofluorescence in epithelial cells from patients with rhinitis, the authors conclude that junctional protein expression is directly inhibited by HDACs in the inflamed epithelium and that blocking HDAC activity can restore junctional protein expression and thus barrier function back to normal. Reduced E-cadherin expression is a feature of epithelial-to-mesenchymal transition, which is a hallmark of malignant transformation. [...]reversal of epithelial-to-mesenchymal transition and restoration of epithelial cell barrier function provide one mechanism explaining the potential efficacy of HDAC inhibitors in treating both epithelial tumors and epithelial dysfunction in patients with allergic airway inflammation. [...]it has been suggested that these proteins are better called lysine deacetylases (“KDACs”) to reflect their broad substrate specificity.8 In future studies, it will be important to determine whether the reduced expression of junctional proteins in epithelial cells from patients with asthma and rhinitis is associated with changes in chromatin structure at the respective genes.