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Liver injury in acute hepatitis A is associated with decreased frequency of regulatory T cells caused by Fas-mediated apoptosis

DC FieldValueLanguage
dc.contributor.author김자경-
dc.contributor.author박준용-
dc.contributor.author이정일-
dc.date.accessioned2015-12-28T11:17:40Z-
dc.date.available2015-12-28T11:17:40Z-
dc.date.issued2015-
dc.identifier.issn0017-5749-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/139130-
dc.description.abstractOBJECTIVE: Foxp3(+)CD4(+)CD25(+) regulatory T cells (Tregs) control immune responses, but their role in acute viral hepatitis remains elusive. Herein, we investigated alteration in the peripheral blood Treg population during acute hepatitis A (AHA) and its implication in the immune-mediated liver injury. DESIGN: The study included 71 patients with AHA, and peripheral blood mononuclear cells (PBMCs) were isolated. The suppressive activity of Treg population was determined by assessing anti-CD3/CD28-stimulated proliferation of Treg-depleted and reconstituted PBMCs. Treg cell frequency, phenotype and apoptosis in PBMCs were analysed by flow cytometry. RESULTS: The frequency of circulating Tregs was reduced during AHA. Moreover, the suppressive activity of the total Treg pool in the peripheral blood was attenuated during AHA. Treg frequency and suppressive activity of the Treg population inversely correlated with the serum alanine aminotransferase level. Fas was overexpressed on Tregs during AHA, suggesting their susceptibility to Fas-induced apoptosis. Indeed, increased apoptotic death was observed in Tregs of patients with AHA compared with healthy controls. In addition, agonistic anti-Fas treatment further increased apoptotic death of Tregs from patients with AHA. The decreased Treg frequency and Fas overexpression on Tregs were not observed in other acute liver diseases such as acute hepatitis B, acute hepatitis C and toxic/drug-induced hepatitis. CONCLUSIONS: The size of the Treg pool was contracted during AHA, resulting from apoptosis of Tregs induced by a Fas-mediated mechanism. Decrease in Treg numbers led to reduced suppressive activity of the Treg pool and consequently resulted in severe liver injury during AHA.-
dc.description.statementOfResponsibilityopen-
dc.format.extent1303~1313-
dc.relation.isPartOfGUT-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAcute Disease-
dc.subject.MESHAdult-
dc.subject.MESHAntiviral Agents/adverse effects*-
dc.subject.MESHAntiviral Agents/therapeutic use-
dc.subject.MESHApoptosis/immunology*-
dc.subject.MESHChemical and Drug Induced Liver Injury/etiology*-
dc.subject.MESHChemical and Drug Induced Liver Injury/immunology-
dc.subject.MESHChemical and Drug Induced Liver Injury/pathology-
dc.subject.MESHFemale-
dc.subject.MESHFlow Cytometry-
dc.subject.MESHHepatitis A/drug therapy-
dc.subject.MESHHepatitis A/immunology*-
dc.subject.MESHHumans-
dc.subject.MESHImmunity, Cellular*-
dc.subject.MESHMale-
dc.subject.MESHT-Lymphocytes, Regulatory/immunology*-
dc.titleLiver injury in acute hepatitis A is associated with decreased frequency of regulatory T cells caused by Fas-mediated apoptosis-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Internal Medicine (내과학)-
dc.contributor.googleauthorJa Kyung Kim-
dc.contributor.googleauthorJung Il Lee-
dc.contributor.googleauthorMin Kyung Jung-
dc.contributor.googleauthorPil Soo Sung-
dc.contributor.googleauthorDong Yeop Chang-
dc.contributor.googleauthorHyun Woong Lee-
dc.contributor.googleauthorJeewon Lee-
dc.contributor.googleauthorYoon Seok Choi-
dc.contributor.googleauthorJun Yong Park-
dc.contributor.googleauthorHana Park-
dc.contributor.googleauthorJae Youn Cheong-
dc.contributor.googleauthorKyung Suk Suh-
dc.contributor.googleauthorHyung Joon Kim-
dc.contributor.googleauthorJune Sung Lee-
dc.contributor.googleauthorKyung Ah Kim-
dc.contributor.googleauthorEui Cheol Shin-
dc.identifier.doi10.1136/gutjnl-2013-306213-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA00852-
dc.contributor.localIdA01675-
dc.contributor.localIdA03122-
dc.relation.journalcodeJ00953-
dc.identifier.eissn1468-3288-
dc.identifier.pmid25007815-
dc.identifier.urlhttp://gut.bmj.com/content/64/8/1303-
dc.subject.keywordACUTE HEPATITIS-
dc.subject.keywordAPOPTOSIS-
dc.subject.keywordHEPATITIS A-
dc.subject.keywordIMMUNE-MEDIATED LIVER DAMAGE-
dc.subject.keywordIMMUNOLOGY IN HEPATOLOGY-
dc.contributor.alternativeNameKim, Ja Kyung-
dc.contributor.alternativeNamePark, Jun Yong-
dc.contributor.alternativeNameLee, Jung Il-
dc.contributor.affiliatedAuthorKim, Ja Kyung-
dc.contributor.affiliatedAuthorPark, Jun Yong-
dc.contributor.affiliatedAuthorLee, Jung Il-
dc.rights.accessRightsfree-
dc.citation.volume64-
dc.citation.number8-
dc.citation.startPage1303-
dc.citation.endPage1313-
dc.identifier.bibliographicCitationGUT, Vol.64(8) : 1303-1313, 2015-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers

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