Rongtao Lai1, Xiaogang Xiang1, Ruidong Mo1, Rebecca Bao2, Peng Wang1, Simin Guo1, Gangde Zhao1, Honglian Gui1, Hui Wang1, Shisan Bao3, Qing Xie4. 1. Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. 2. Discipline of Pathology, Bosch Institute and School of Medical Sciences, University of Sydney, Sydney, NSW, Australia. 3. Discipline of Pathology, Bosch Institute and School of Medical Sciences, University of Sydney, Sydney, NSW, Australia. Electronic address: bob.bao@sydney.edu.au. 4. Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. Electronic address: xieqingrjh@163.com.
Abstract
BACKGROUND & AIMS: 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.
BACKGROUND & AIMS: 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.