title: Role of interleukin-23 in monocyte-derived dendritic cells of HBV-related acute-on-chronic liver failure and its correlation with the severity of liver damage.
abstract: BACKGROUND
  The role of interleukin-23 (IL-23) in monocyte-derived dendritic cells (MoDCs) from hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) patients remains unclear. The aim of this study was to observe the correlation between the activation of the IL-23 signaling pathway and the prognosis of HBV-ACLF patients.
  
  
  METHODS
  The baseline levels of serum IL-6, IL-12, IL-17, IL-23, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) from immune tolerant (IT), chronic hepatitis B (CHB), HBV-ACLF patients and healthy individuals who served as healthy controls (HCs) were analyzed using the Luminex system, whereas serum IL-23 from HBV-ACLF patients was measured by ELISA before and after treatment. Purified monocytes were isolated from peripheral blood and were induced into MoDCs, IL-23, IL-23R, NF-κB and TRAF6 expression in MoDCs from 4 groups was analyzed using real-time PCR, and IL-23R and intracellular IL-23 were evaluated by flow cytometry.
  
  
  RESULTS
  Serum IL-6, IL-12, IL-17, IL-23 and TNF-α levels were upregulated in HBV-ACLF patients compared with IT patients, CHB patients and HCs (P<0.05 for all). Serum IL-23 was closely correlated with elevated serum IL-17 in HBV-ACLF patients (r=0.5935, P<0.0001). Moreover, IL-23 and IL-23R levels were significantly upregulated in MoDCs from patients with CHB or HBV-ACLF compared with HCs, and further upregulation of IL-23 and IL-23R was observed in HBV-ACLF patients compared to CHB patients (P<0.05 for all). IL-23 expression was markedly enhanced and was correlated with elevated NF-κB and TRAF6 in MoDCs from HBV-ACLF patients (P<0.05 for both). Linear correlation analysis demonstrated significant correlations between the expression of IL-23 and disease severity markers (MELD scoring system, international normalized ratio, prothrombin time and total bilirubin, r=0.6874, r=0.6475, r=0.6249, r=0.3771, respectively, P<0.05 for all) for individual HBV-ACLF patients, and IL-23 levels were significantly upregulated in non-survival HBV-ACLF patients compared with survival HBV-ACLF patients (P<0.05).
  
  
  CONCLUSIONS
  IL-23 in serum and MoDCs is significantly elevated in HBV-ACLF patients, TRAF6/NF-κB may play a role in IL-23 production by MoDCs in HBV-ACLF patients and high pre-treatment IL-23 levels in MoDCs are associated with mortality in HBV-ACLF patients.
authors.affiliation: Department of infectious diseases, Fudan university, Huashan hospital, 200040 Shanghai, China.
authors.forename: Suxia
authors.initials: S
authors.lastname: Bao
authors.affiliation: Department of infectious diseases, Fudan university, Huashan hospital, 200040 Shanghai, China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of infectious diseases, Fudan university, Huashan hospital, 200040 Shanghai, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of infectious diseases, Fudan university, Huashan hospital, 200040 Shanghai, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of infectious diseases, Fudan university, Huashan hospital, 200040 Shanghai, China.
authors.forename: Mingquan
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of infectious diseases, Fudan university, Huashan hospital, 200040 Shanghai, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Cheng
authors.affiliation: Department of infectious diseases, Fudan university, Huashan hospital, 200040 Shanghai, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of infectious diseases, Fudan university, Huashan hospital, 200040 Shanghai, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Lu
authors.affiliation: Department of infectious diseases, Fudan university, Huashan hospital, 200040 Shanghai, China.
authors.forename: Mengqi
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of infectious diseases, Fudan university, Huashan hospital, 200040 Shanghai, China.
authors.forename: Qingxia
authors.initials: Q
authors.lastname: Ling
authors.affiliation: Department of infectious diseases, Fudan university, Huashan hospital, 200040 Shanghai, China.
authors.forename: Kangkang
authors.initials: K
authors.lastname: Yu
authors.affiliation: Department of infectious diseases, Fudan university, Huashan hospital, 200040 Shanghai, China.
authors.forename: Shengshen
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of infectious diseases, Fudan university, Huashan hospital, 200040 Shanghai, China. Electronic address: gfshi@shmu.edu.cn.
authors.forename: Guangfeng
authors.initials: G
authors.lastname: Shi
mesh_terms: D065290:Acute-On-Chronic Liver Failure / Q000276:immunology* / Q000401:mortality / Q000473:pathology*; D000328:Adult; D003713:Dendritic Cells / Q000737:chemistry*; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000097:blood; D053759:Interleukin-23 / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D008099:Liver / Q000473:pathology*; D008297:Male; D009000:Monocytes / Q000276:immunology*; D016328:NF-kappa B / Q000032:analysis; D018123:Receptors, Interleukin / Q000032:analysis; D048029:TNF Receptor-Associated Factor 6 / Q000032:analysis
chemical_list: C515500:IL23R protein, human; D020381:Interleukin-17; D053759:Interleukin-23; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D018123:Receptors, Interleukin; D048029:TNF Receptor-Associated Factor 6; C000604754:Tifab protein, human