{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T05:56:01Z","timestamp":1783662961399,"version":"3.55.0"},"reference-count":38,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Ther Adv Respir Dis"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:sec><jats:title>Background:<\/jats:title><jats:p> The class III NAD-dependent histone deacetylase (HDAC) sirtuin 1 (SIRT1) is an important regulator of senescence, aging, and inflammation. SIRT1de-acetylates chromatin histones, thereby silencing inflammatory gene transcription. We have reported increased steroid-resistant senescent pro-inflammatory CD28nullCD8+ T cells in patients with chronic obstructive pulmonary disease (COPD). We hypothesized that SIRT1 is reduced in these cells in COPD, and that treatment with SIRT1 activators (resveratrol, curcumin) and agents preventing NAD depletion (theophylline) would upregulate SIRT1 and reduce pro-inflammatory cytokine expression in these steroid-resistant cells. <\/jats:p><\/jats:sec><jats:sec><jats:title>Methods:<\/jats:title><jats:p> Blood was collected from n\u2009=\u200910 COPD and n\u2009=\u200910 aged-matched controls. Expression of CD28, SIRT1, and pro-inflammatory cytokines was determined in CD8+ and CD8\u2013 T and natural killer T (NKT)-like cells cultured in the presence of \u00b11\u2009\u00b5M prednisolone, \u00b15\u2009mg\/L theophylline, \u00b11\u2009\u00b5M curcumin, \u00b125\u2009\u00b5M resveratrol, using flow cytometry and immunofluorescence. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p> There was an increase in the percentage of CD28nullCD8+ T and NKT-like cells in COPD patients compared with controls. Decreased SIRT1 expression was identified in CD28nullCD8+T and NKT-like cells compared with CD28+ counterparts from both patients and controls (e.g. CD28null 11\u2009\u00b1\u20093% versus CD28+ 57\u2009\u00b1\u20099%). Loss of SIRT1 was associated with increased production of IFN\u03b3 and TNF\u03b1, steroid resistance, and disease severity. SIRT1 expression was upregulated in the presence of all drugs and was associated with a decrease in steroid resistance and IFN\u03b3 and TNF\u03b1 production by CD28nullCD8+T and NKT-like cells. The presence of the SIRT1 inhibitor, EX-527 negated [by 92\u2009\u00b1\u200912% (median\u2009\u00b1\u2009SEM)] the effect of the SIRT1 activator SRT720 on the percentage of CD8+ T cells producing IFN\u03b3 and TNF\u03b1. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions:<\/jats:title><jats:p> Steroid resistance in pro-inflammatory CD28nullCD8+ T and NKT-like cells is associated with decreased SIRT1 expression. Treatment with prednisolone, in combination with theophylline, curcumin or resveratrol increases SIRT1 expression, restores steroid sensitivity, and inhibits pro-inflammatory cytokine production from these cells and may reduce systemic inflammation in COPD. The reviews of this paper are available via the supplemental material section. <\/jats:p><\/jats:sec>","DOI":"10.1177\/1753466620905280","type":"journal-article","created":{"date-parts":[[2020,4,9]],"date-time":"2020-04-09T10:11:38Z","timestamp":1586427098000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":26,"title":["Lymphocyte senescence in COPD is associated with decreased sirtuin 1 expression in steroid resistant pro-inflammatory lymphocytes"],"prefix":"10.1177","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8689-963X","authenticated-orcid":false,"given":"Greg","family":"Hodge","sequence":"first","affiliation":[{"name":"Lung Research, Department of Thoracic Medicine, Royal Adelaide Hospital, AHMS building, North Terrace, Adelaide, South Australia 5000, Australia"},{"name":"Department of Medicine, University of Adelaide, Adelaide, South Australia, 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