{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T17:15:15Z","timestamp":1781025315436,"version":"3.54.1"},"reference-count":18,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2018,10,29]],"date-time":"2018-10-29T00:00:00Z","timestamp":1540771200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,1,13]]},"abstract":"<jats:title>Summary<\/jats:title>\n               <jats:p>Immunosuppression therapies including corticosteroids fail to prevent bronchiolitis obliterans syndrome (BOS), primarily a disease of the small airways, following lung transplantation. We reported increases in steroid-resistant proinflammatory lymphocytes and their loss of histone deacetylase 2 (HDAC2), an important mediator of steroid action, in the blood of stable lung transplant recipients. We noted similar increases in the steroid-resistant lymphocytes in both the blood and small airways in BOS compared with the large airways. We hypothesized that these small airway cells would also exhibit a loss of HDAC2, and that these changes could be reversed by treatment with theophylline (HDAC2 activator). Blood, bronchoalveolar lavage and large and small airway brushings were collected from lung transplant patients with BOS (n = 12) or stable lung function (n = 18) and healthy aged-matched controls (n = 13). Intracellular proinflammatory cytokines [interferon (IFN-\u03b3) and tumour necrosis factor (TNF)-\u03b1 and HDAC2 were measured in CD8+ T, natural killer (NK) T-like and NK cells from cultured small airway brushings \u00b1 5 mg\/l theophylline \u00b1 1 \u00b5M prednisolone using flow cytometry. Increased small airway CD8 T, NK T-like and NK cells were identified in BOS versus stable transplant and controls. In BOS, these cells exhibited increased IFN-\u03b3\/TNF-\u03b1 and a loss of HDAC2. HDAC2 expression by small airway CD8+ T cells correlated with forced expiratory volume in 1 s (FEV1) (R = 0\u00b7880, P = 0\u00b7031). Theophylline and prednisolone synergistically up-regulated HDAC2 in CD8+ T cells. BOS is associated with loss of HDAC2 from steroid-resistant proinflammatory CD8+ T, NK T-like and NK cells in the small airways. Therapeutically increasing HDAC2 in these lymphocytes may reduce steroid resistance and improve graft survival.<\/jats:p>","DOI":"10.1111\/cei.13221","type":"journal-article","created":{"date-parts":[[2018,10,10]],"date-time":"2018-10-10T19:25:53Z","timestamp":1539199553000},"page":"277-285","source":"Crossref","is-referenced-by-count":7,"title":["BOS is associated with decreased HDAC2 from steroid resistant lymphocytes in the small airways"],"prefix":"10.1093","volume":"195","author":[{"given":"G","family":"Hodge","sequence":"first","affiliation":[{"name":"Lung Research, Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia"},{"name":"Department of Medicine, University of Adelaide, Adelaide, South Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Hodge","sequence":"additional","affiliation":[{"name":"Lung Research, Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia"},{"name":"Department of Medicine, University of Adelaide, Adelaide, South Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Yeo","sequence":"additional","affiliation":[{"name":"Lung Research, Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia"},{"name":"Department of Medicine, University of Adelaide, Adelaide, South Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Lung Research, Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia"},{"name":"Department of Medicine, University of Adelaide, Adelaide, South Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Hopkins","sequence":"additional","affiliation":[{"name":"Lung Research, Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Liu","sequence":"additional","affiliation":[{"name":"Lung Research, Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia"},{"name":"Department of Medicine, University of Adelaide, Adelaide, South Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C L","family":"Holmes-Liew","sequence":"additional","affiliation":[{"name":"Lung Research, Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia"},{"name":"Department of Medicine, University of Adelaide, Adelaide, South Australia, Australia"},{"name":"South Australian Lung Transplant Service, Adelaide, South Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Holmes","sequence":"additional","affiliation":[{"name":"Lung Research, Department of Thoracic 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