title: Genomewide Histone H3 Lysine 9 Acetylation Profiling in CD4+ T Cells Revealed Endoplasmic Reticulum Stress Deficiency in Patients with Acute-on-chronic Liver Failure.
abstract: Acute-on-chronic liver failure (ACLF) displayed 'sepsis-like' immune paralysis. Little is known about the role of CD4+ T lymphocytes, the primary regulator of innate and adopted immune system, played in ACLF. Acetylation of histone H3 lysine 9 (H3K9ac), a key epigenetic modification, tightly controls gene transcription. Whether and how does H3K9ac modification regulate CD4+ T cells in ACLF remains unclear. PBMCs were isolated from patients with ACLF, immune tolerance of chronic hepatitis B (CHB-T) and immune active of chronic hepatitis B (CHB-A). Then, CD4+ T lymphocytes were purified by magnetic microbeads, and the purity was confirmed by flow cytometry. H3K9ac variations were analysed in CD4+ T cells using chromatin immunoprecipitation microarray and then confirmed by quantitative PCR. Whole-genome H3K9 acetylation analyses were conducted by bioinformatics. A total of 70 genes were differently modified in H3K9ac between CHB-A and ACLF groups, while 44 genes were differently modified in H3K9ac between CHB-T and ACLF groups. Clustering algorithm analysis showed patients with ACLF displayed 'sepsis-like' immune paralysis. Functional analysis showed endoplasmic reticulum (ER) stress, or downstream pathway-related genes, such as BIP, ATF4, PER1, CSNK1D, IRF3, BNIP1, AKT1 and UBC, were differentially modified in ACLF. We profiled H3K9 acetyl modification in CD4+ T lymphocytes from HBV-infected patients with three different immune states, that is ACLF, immune tolerance and immune active phases. ACLF displayed 'sepsis-like' immune paralysis. ER stress in CD4+ T lymphocytes attributed to ACLF. This study provides some useful clues for revealing the mechanisms underlying ACLF.
authors.affiliation: Department of Infectious Diseases, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
authors.forename: L
authors.initials: L
authors.lastname: Jin
authors.affiliation: Department of Infectious Diseases, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou City, Guangdong Province, China.
authors.forename: K
authors.initials: K
authors.lastname: Wang
authors.affiliation: The Eighth Hospital, Xi'an, Shaanxi Province, China.
authors.forename: H
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Infectious Diseases, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
authors.forename: T
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Infectious Diseases, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.affiliation: The Eighth Hospital, Xi'an, Shaanxi Province, China.
authors.forename: X
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Infectious Diseases, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.affiliation: Xi'an children's hospital, Xi'an, Shaanxi Province, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Infectious Diseases, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
authors.forename: D
authors.initials: D
authors.lastname: Du
authors.affiliation: Department of Infectious Diseases, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Infectious Diseases, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
authors.forename: Y
authors.initials: Y
authors.lastname: He
mesh_terms: D000107:Acetylation; D065290:Acute-On-Chronic Liver Failure / Q000235:genetics / Q000276:immunology*; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D047369:Chromatin Immunoprecipitation; D016172:DNA Fingerprinting; D059865:Endoplasmic Reticulum Stress / Q000235:genetics / Q000276:immunology; D005260:Female; D016678:Genome; D016174:Hepacivirus / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000235:genetics / Q000276:immunology*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics / Q000276:immunology; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology*; D008239:Lysine / Q000378:metabolism; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D005810:Multigene Family / Q000235:genetics; D010770:Phosphotransferases / Q000235:genetics; D018805:Sepsis / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics; D055815:Young Adult
chemical_list: D006657:Histones; D014157:Transcription Factors; D010770:Phosphotransferases; D008239:Lysine