title: Association between histone hyperacetylation status in memory T lymphocytes and allergen-induced eosinophilic airway inflammation.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Pneumology Group, Department of Integrated Traditional Chinese and Western Medicine, State Key Laboratory of Biotherapy of China, West China Hospital, Sichuan University, Chengdu, China.|Pneumology Group, Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Hong Ping
authors.initials: HP
authors.lastname: Zhang
authors.affiliation: Pneumology Group, Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Pneumology Group, Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Juan Juan
authors.initials: JJ
authors.lastname: Fu
authors.affiliation: Pneumology Group, Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Fan
authors.affiliation: Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Zeng Li
authors.initials: ZL
authors.lastname: Wang
authors.affiliation: Pneumology Group, Department of Integrated Traditional Chinese and Western Medicine, State Key Laboratory of Biotherapy of China, West China Hospital, Sichuan University, Chengdu, China.|Pneumology Group, Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
mesh_terms: D000107:Acetylation; D000485:Allergens / Q000276:immunology; D048729:Anacardic Acids / Q000494:pharmacology; D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D018929:Cell Culture Techniques; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004804:Eosinophils; D005938:Glucocorticoids / Q000494:pharmacology; D051548:Histone Acetyltransferases / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006877:Hydroxamic Acids / Q000494:pharmacology; D007249:Inflammation / Q000276:immunology; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*
chemical_list: D000485:Allergens; D048729:Anacardic Acids; D016207:Cytokines; D005938:Glucocorticoids; D006657:Histones; D006877:Hydroxamic Acids; C088115:anacardic acid; C012589:trichostatin A; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases
keywords: airway inflammation; asthma; glucocorticoids; histone deacetylation; memory T lymphocytes