title: Protective effect of Th22 cells and intrahepatic IL-22 in drug induced hepatocellular injury.
abstract: OBJECTIVE
  Th22 cells regulate host immunity against pathogenic invasion, including protecting host against chronic hepatitis B; however, the relationship between drug induced liver injury (DILI) and Th22/Th17 cells is still unclear. We investigated the role of Th22 cells in DILI development.
  
  
  METHODS
  The frequencies of peripheral Th22/Th17/Th1 cells and intrahepatic IL-22/IL-17 production from DILI, non-DILI liver diseases, and healthy controls were examined. Plasma IL-22/IL-17 and the related cytokines were determined in DILI patients at week 0 (defined as the occurrence of liver injury within 7days), 4 and 24. Multivariable stepwise logistic regression was applied to explore the associations between various factors and recovery of DILI.
  
  
  RESULTS
  The frequencies of Th22/Th17 cells were significantly higher in DILI onset patients than HC. Significant increase of Th22 cells and the related cytokines levels was observed in DILI with hepatocellular injury type. There was a positive correlation between intrahepatic IL-22 level and liver regeneration. Plasma IL-22 level was higher in DILI patients with improved liver function than unimproved function. Multivariable analysis showed that the odds ratio (OR) of plasma IL-22 at 4weeks was 1.054 [95% confidence interval (CI), 1.012, 1.124].
  
  
  CONCLUSIONS
  Increased peripheral and intrahepatic IL-22-secreting cells are detected in DILI. Th22 and its related cytokines might be hepato-protective, which might provide new perspective for understanding the immunopathogenesis of DILI. Plasma IL-22 might be a reliable indicator to evaluate the prognosis of DILI and provide a novel therapeutic target for DILI treatment.
authors: Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Rongtao
authors: R
authors: Lai
authors: Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Xiaogang
authors: X
authors: Xiang
authors: Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Ruidong
authors: R
authors: Mo
authors: Discipline of Pathology, Bosch Institute and School of Medical Sciences, University of Sydney, Sydney, NSW, Australia.
authors: Rebecca
authors: R
authors: Bao
authors: Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Peng
authors: P
authors: Wang
authors: Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Simin
authors: S
authors: Guo
authors: Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Gangde
authors: G
authors: Zhao
authors: Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Honglian
authors: H
authors: Gui
authors: Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Hui
authors: H
authors: Wang
authors: Discipline of Pathology, Bosch Institute and School of Medical Sciences, University of Sydney, Sydney, NSW, Australia. Electronic address: bob.bao@sydney.edu.au.
authors: Shisan
authors: S
authors: Bao
authors: Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. Electronic address: xieqingrjh@163.com.
authors: Qing
authors: Q
authors: Xie
mesh_terms: D056486:Chemical and Drug Induced Liver Injury / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007378:Interleukins / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D007378:Interleukins; D000097043:Interleukin-22
keywords: DILI; IL-22; Protection; Th17 cells; Th22 cells