title: Inhibition of SATB1 expression in regulatory T cells contributes to hepatitis B virus-related chronic liver inflammation.
abstract: Regulatory T cells (Tregs) contribute to the pathogenesis of chronic hepatitis B (CHB). Special AT-rich sequence-binding protein 1 (SATB1) may be a key component of this process. In the present study, Tregs and conventional T cells (Tconvs) were isolated by magnetic cell sorting of peripheral blood from CHB patients (n=57), individuals with resolved hepatitis B virus (HBV) infections (n=15), and healthy controls (n=29). SATB1 expression was studied by reverse transcription-quantitative PCR, flow cytometry and immunofluorescence microscopy, and the correlation of SATB1 expression to the expression of liver inflammation serum markers and the HBV DNA load was assessed. CHB patients showed significantly reduced SATB1 expression in Tregs than healthy controls and individuals with resolved HBV infections. Moreover, SATB1 expression in Tregs was significantly lower than in Tconvs of patients with chronic HBV infection. Serum HBV DNA and liver inflammation markers were inversely correlated to the SATB1 mRNA level in Tregs. Antiviral treatment was accompanied by increased expression of the SATB1 gene in Tregs. Thus, Tregs from CHB patients have reduced levels of SATB1, which is resolved with antiviral therapy. Inhibition of SATB1 expression may impair the hepatic inflammatory response and contribute to HBV persistence.
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Xue-Fen
authors.initials: XF
authors.lastname: Li
authors.affiliation: Department of Laboratory Medicine, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Tian
authors.affiliation: Department of Laboratory Medicine, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Yi-Yin
authors.initials: YY
authors.lastname: Wang
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Hai-Shen
authors.initials: HS
authors.lastname: Kong
authors.affiliation: Department of Laboratory Medicine, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Yue-Jiao
authors.initials: YJ
authors.lastname: Dong
authors.affiliation: Department of Laboratory Medicine, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Qiao-Yun
authors.initials: QY
authors.lastname: Zhu
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Ni
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D006801:Humans; D016130:Immunophenotyping; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology / Q000627:therapeutic use; D008111:Liver Function Tests; D008297:Male; D036961:Matrix Attachment Region Binding Proteins / Q000235:genetics*; D011092:Polyethylene Glycols / Q000494:pharmacology / Q000627:therapeutic use; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D019562:Viral Load; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D036961:Matrix Attachment Region Binding Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; C076189:SATB1 protein, human; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b