title: Impact of HBeAg on the maturation and function of dendritic cells.
abstract: OBJECTIVE
  HBV infection typically leads to chronic hepatitis in newborns and some adults with weakened immune systems. The mechanisms by which virus escapes immunity remain undefined. Regulatory dendritic cells (DCregs) contributing to immune escape have been described. We wondered whether or not HBeAg as an immunomodulatory protein could induce DCreg which might subsequently result into HBV persistence.
  
  
  METHODS
  The immunophenotyping, T-cell activation and cytokine production were analyzed in HBeAg-treated DCs from normal or cyclophosphamide (Cy)-induced immunocompromised mice.
  
  
  RESULTS
  HBeAg tended to promote bone marrow derived DCs (BMDCs) from Cy-treated mice into CD11b(high)PIR-B(+) regulatory DCs exhibiting the lowest T-cell stimulatory capacity and interleukin (IL)-12p70 production compared with controls. Neutralization of IL-10 significantly inhibited the regulatory effect of these DCs on T-cell stimulation of mature DCs. After lipopolysaccharides (LPS) stimulation, marked phosphorylation of Akt was detected in HBeAg treated DCs from immunocompromised mice. Blocking the PI3K-Akt pathway by LY294002 led to an enhancement of IL-12 production. PI3K signalling pathway appears to be involved in the decreased IL-12 secretion by HBeAg treated DCs.
  
  
  CONCLUSIONS
  These findings suggest that HBeAg may program the generation of a new DC subset with regulatory capacity under the condition of immunosuppression, which may presumably contribute to the persistent HBV infection.
authors.affiliation: Department of Ultrasonography, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China.
authors.forename: Songsong
authors.initials: S
authors.lastname: Lan
authors.affiliation: Department of Gastroenterology, Wenzhou People's Hospital, Wenzhou, 325000, Zhejiang Province, China.
authors.forename: Lecan
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China.
authors.forename: Xiuyan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China. Electronic address: wzfywjm@163.com.
authors.forename: Jinming
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China.
authors.forename: Xianfan
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China.
authors.forename: Wenzhi
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Huang
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000276:immunology; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000276:immunology*; D006513:Hepatitis B e Antigens / Q000276:immunology*; D019694:Hepatitis B, Chronic; D006801:Humans; D016867:Immunocompromised Host; D016130:Immunophenotyping; D007378:Interleukins / Q000378:metabolism*; D008070:Lipopolysaccharides; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D006513:Hepatitis B e Antigens; D007378:Interleukins; D008070:Lipopolysaccharides; D019869:Phosphatidylinositol 3-Kinases
keywords: Cell differentiation; Chronic hepatitis B; HBeAg; Immune regulation; Regulatory dendritic cells