{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T14:41:59Z","timestamp":1789396919682,"version":"build-2803163510"},"reference-count":46,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2013,3,29]],"date-time":"2013-03-29T00:00:00Z","timestamp":1364515200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Alcoholism Clin &amp; Exp Res"],"published-print":{"date-parts":[[2013,8]]},"abstract":"Background<\/jats:title>Development of alcoholic hepatitis (AH<\/jats:styled-content>) may be favored by the activation of the innate immune response. Recently, decreased numbers of circulating regulatory T<\/jats:styled-content> cells (T<\/jats:styled-content>regs) have been reported in diseases associated with an immune activation status, but no studies have focused so far, in investigating the distribution of T<\/jats:styled-content>regs in chronic alcoholism and its potential association with liver disease. Here, we analyzed for the first time the frequency of peripheral blood (PB<\/jats:styled-content>) T<\/jats:styled-content>regs and T<\/jats:styled-content>reg subsets in AH<\/jats:styled-content> and its relationship with the production of inflammatory cytokines by PB<\/jats:styled-content> monocytes and dendritic cells (DC<\/jats:styled-content>s).<\/jats:p><\/jats:sec>Methods<\/jats:title>PB samples from 25 male patients with AH<\/jats:styled-content> were studied; in parallel, 15 male chronic alcoholic patients without liver disease (AWLD<\/jats:styled-content>) and 17 male healthy donors were also studied, as controls. The distribution of CD<\/jats:styled-content>4+<\/jats:sup>CD<\/jats:styled-content>25hi<\/jats:sup>CD<\/jats:styled-content>127\u2212\/lo<\/jats:sup> Tregs and their maturation subsets (na\u00efve, central memory, and peripheral memory T<\/jats:styled-content>regs) was analyzed by flow cytometry. Spontaneous and in vitro\u2010stimulated production of inflammatory cytokines by PB<\/jats:styled-content> monocytes and DC<\/jats:styled-content>s was analyzed by flow cytometry at the cytoplasmic level.<\/jats:p><\/jats:sec>Results<\/jats:title>Patients with AH<\/jats:styled-content> showed decreased (p<\/jats:italic>\u00a0<\u00a00.05) numbers of PB CD<\/jats:styled-content>4+<\/jats:sup>CD<\/jats:styled-content>25hi<\/jats:sup>CD<\/jats:styled-content>127\u2212\/lo<\/jats:sup> Tregs at the expense of all maturation\u2010associated subsets, while AWLD<\/jats:styled-content> and healthy subjects showed a similar (p<\/jats:italic>\u00a0>\u00a00.05) distribution of PB CD<\/jats:styled-content>4+<\/jats:sup>CD<\/jats:styled-content>25hi<\/jats:sup>CD<\/jats:styled-content>127\u2212\/lo<\/jats:sup> T<\/jats:styled-content>regs. Interestingly, significantly increased amounts of spontaneously produced inflammatory cytokines were found among circulating monocyte\u2010derived DC<\/jats:styled-content>s and monocytes from AH<\/jats:styled-content> (and AWLD<\/jats:styled-content>) patients in comparison with healthy donors. Conversely, the ability of these cell subsets to produce cytokines after in vitro stimulation was lower (p<\/jats:italic>\u00a0<\u00a00.05) in AH<\/jats:styled-content> versus the 2 control groups.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>PB CD<\/jats:styled-content>4+<\/jats:sup>CD<\/jats:styled-content>25hi<\/jats:sup>CD<\/jats:styled-content>127\u2212\/lo<\/jats:sup> T<\/jats:styled-content>regs are significantly decreased in patients with AH<\/jats:styled-content> when compared to both healthy and AWLD<\/jats:styled-content>; this may contribute to explain the more pronounced activation of the innate immune response observed in AH<\/jats:styled-content>, as reflected by an increased secretion of inflammatory cytokines by PB DC<\/jats:styled-content>s and monocytes, and could facilitate the development of liver disease.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.12095","type":"journal-article","created":{"date-parts":[[2013,3,29]],"date-time":"2013-03-29T15:14:17Z","timestamp":1364570057000},"page":"1361-1369","source":"Crossref","is-referenced-by-count":42,"title":["Decreased Peripheral Blood CD<\/scp>4+<\/sup>\/CD<\/scp>25+<\/sup> Regulatory T<\/scp> Cells in Patients with Alcoholic Hepatitis"],"prefix":"10.1111","volume":"37","author":[{"given":"Julia","family":"Almeida","sequence":"first","affiliation":[{"name":"Cancer Research Center IBSAL and Cytometry Service University of Salamanca Salamanca Spain"},{"name":"Department of Medicine University of Salamanca Salamanca Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Angeles","family":"Polvorosa","sequence":"additional","affiliation":[{"name":"Alcoholism Unit Department of Internal Medicine University Hospital of Salamanca and IBSAL Salamanca Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arturo","family":"Gonzalez\u2010Quintela","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University Hospital of Santiago de Compostela Santiago de Compostela Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Marcos","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Salamanca Salamanca Spain"},{"name":"Alcoholism Unit Department of Internal Medicine University Hospital of Salamanca and IBSAL Salamanca Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Pastor","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Salamanca Salamanca Spain"},{"name":"Alcoholism Unit Department of Internal Medicine University Hospital of Salamanca and IBSAL Salamanca Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Luisa","family":"Hernandez Cerce\u00f1o","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry University Hospital of Salamanca Salamanca Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Orfao","sequence":"additional","affiliation":[{"name":"Cancer Research Center IBSAL and Cytometry Service University of Salamanca Salamanca Spain"},{"name":"Department of Medicine University of Salamanca Salamanca Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco\u2010Javier","family":"Laso","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Salamanca Salamanca Spain"},{"name":"Alcoholism Unit Department of Internal Medicine University Hospital of Salamanca and IBSAL Salamanca 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