Association between histone hyperacetylation status in memory T lymphocytes and allergen‐induced eosinophilic airway inflammation. Issue 5 (17th March 2016)

• Record Type: Journal Article
• Authors: Zhang, Hong Ping; Wang, Lei; Fu, Juan Juan; Fan, Tao; Wang, Zeng Li; Wang, Gang
• Is Part Of: Respirology. Volume 21:Issue 5(2016)
• Page Start: 850
• Page End: 857
• Publication Date: 2016-03-17
• Subjects: airway inflammation -- asthma -- glucocorticoids -- histone deacetylation -- memory T lymphocytes; Respiratory organs -- Diseases -- Periodicals; Respiratory organs -- Periodicals; 612.2
• DOI: 10.1111/resp.12774
• Languages: English
• ISSNs: 1323-7799

Abstract

Abstract: Background and objective: T lymphocytes, which are characterized by longevity and immune memory, play an important role in airway inflammation in asthma. Here, we assessed the association between immune memory and histone deacetylation and/or acetylation status. Methods: CD4 + CD45RB low cells (memory T (Tm)) obtained from the spleens of asthma mice models were co‐cultured with glucocorticoids (GCs), trichostatin A (TSA) or anacardic acid (AA) and adoptively transferred to naïve mice. Interleukin (IL)‐4, 5 and 13 and IFN‐γ concentrations were measured in culture supernatants and bronchoalveolar lavage fluid (BALF). Histone deacetylase (HDAC) and histone acetyltransferase (HAT) activities and the expression of T‐bet, GATA‐3, HDACs 1–11 and alveolar eosinophilic inflammation index (AEII) were determined in lung tissues. Results: Culture supernatants and the BALF showed similar cytokine profiles. AA and GCs significantly inhibited HAT activity ( P = 0.002 and P = 0.018), whereas TSA inhibited and GCs promoted HDAC activity ( P = 0.004 and P = 0.025). HDACs 7, 9 and 10 were upregulated by AA and GCs (all P < 0.032), while HDAC11 was upregulated by GCs ( P = 0.028). GC‐induced inhibition of Tm histone acetylation alleviated AEII by downregulating IL‐4, 5 and 13, similar to the effect of AA. Conclusion: Histone hyperacetylation status induced by low expression of HDACs 7, 9 and 10 in allergen‐specific Tm cells contributes to eosinophilic airway inflammation. The mechanism by which GCs improve airway inflammation involves the upregulation of HDACs 7, 9, 10 and 11 and especially HDAC‐10. The role of individual HDACs and AA as novel therapeutic agents for allergic asthma needs to be explored in the future. Abstract : Upregulation of histone deacetylase (HDACs 7, 9, 10 and 11 plays a role in the epigenetic mechanism by which glucocorticoids improve allergen‐driven airway inflammation in mice. The therapeutic potential of individual HDACs and anacardic acid for the treatment of allergic asthma needs to be explored in the future.