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Changes in circulating Foxp3(+) regulatory T cells and interleukin-17-producing T helper cells during HBV-related acute-on-chronic liver failure.
World J Gastroenterol 2014; 20(26):8558-71WJ

Abstract

AIM

To longitudinally investigate cytokine gene expression and protein levels in Th17 and Treg cells, to observe T-cell phenotypes during hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACHBLF) and to analyze changes in Th17 and Treg phenotypes during disease progression.

METHODS

We measured the expression of seven Th17/Treg differentiation-related genes and serum concentrations of the corresponding cytokines in 18 ACHBLF, 18 chronic hepatitis B (CHB) disease controls and 10 healthy controls (HCs) by real-time quantitative PCR and enzyme linked immunosorbent assay. Peripheral Th17 and Treg cell frequencies were analyzed by flow cytometry.

RESULTS

From the onset of ACHBLF, patients presented with a conductive Th17 differentiation cytokine environment accompanied by high Th17 frequency and high serum IL-17 levels, which were sustained throughout the disease course. The Treg-related cytokine IL-2 and Foxp3 were also up-regulated from disease onset, and Foxp3 gene expression showed a gradually increasing trend during ACHBLF. The circular phenotype of Treg and Th17 cells showed changes from the onset of ACHGLF. At disease onset, Th17 frequency increased significantly compared with both CHB and HCs, but Treg cell frequency decreased significantly compared with CHB. During the ACHBLF event, Th17 frequency remained higher compared with HCs, but decreased sharply from the peak point to the recovery point; Treg cell frequency increased gradually during the ACHBLF event. Treg and Th17 cell counts correlated with ACHBLF development; in all patients, serum IL-17 levels significantly correlated with patient serum ALT levels. In survivors, Th17 frequency at the onset point and the Treg to Th17 ratio at the peak point correlated with the patient's model for end stage liver disease (MELD) plus sodium (MELD-Na) score. The Treg to Th17 ratio and the Th17 frequency at onset were significant predictors of patient survival. Low Treg/Th17 cell ratios at the onset predicted poor survival. Survivors exhibited an initial decrease in the circulating Treg/Th17 ratio from the onset to the peak time, and subsequently displayed a continuous increase.

CONCLUSION

Treg and Th17 cells showed changes in genes, protein levels and T cell phenotypes during ACHBLF events. An increased Treg/Th17 ratio was associated with the survival of ACHBLF patients.

Authors+Show Affiliations

Xue-Song Liang, Cheng-Zhong Li, Yin Zhou, Wei Yin, Ya-Yun Liu, Wen-Han Fan, Department of Infectious Diseases, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.Xue-Song Liang, Cheng-Zhong Li, Yin Zhou, Wei Yin, Ya-Yun Liu, Wen-Han Fan, Department of Infectious Diseases, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.Xue-Song Liang, Cheng-Zhong Li, Yin Zhou, Wei Yin, Ya-Yun Liu, Wen-Han Fan, Department of Infectious Diseases, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.Xue-Song Liang, Cheng-Zhong Li, Yin Zhou, Wei Yin, Ya-Yun Liu, Wen-Han Fan, Department of Infectious Diseases, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.Xue-Song Liang, Cheng-Zhong Li, Yin Zhou, Wei Yin, Ya-Yun Liu, Wen-Han Fan, Department of Infectious Diseases, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.Xue-Song Liang, Cheng-Zhong Li, Yin Zhou, Wei Yin, Ya-Yun Liu, Wen-Han Fan, Department of Infectious Diseases, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25024610

Citation

Liang, Xue-Song, et al. "Changes in Circulating Foxp3(+) Regulatory T Cells and Interleukin-17-producing T Helper Cells During HBV-related Acute-on-chronic Liver Failure." World Journal of Gastroenterology, vol. 20, no. 26, 2014, pp. 8558-71.
Liang XS, Li CZ, Zhou Y, et al. Changes in circulating Foxp3(+) regulatory T cells and interleukin-17-producing T helper cells during HBV-related acute-on-chronic liver failure. World J Gastroenterol. 2014;20(26):8558-71.
Liang, X. S., Li, C. Z., Zhou, Y., Yin, W., Liu, Y. Y., & Fan, W. H. (2014). Changes in circulating Foxp3(+) regulatory T cells and interleukin-17-producing T helper cells during HBV-related acute-on-chronic liver failure. World Journal of Gastroenterology, 20(26), pp. 8558-71. doi:10.3748/wjg.v20.i26.8558.
Liang XS, et al. Changes in Circulating Foxp3(+) Regulatory T Cells and Interleukin-17-producing T Helper Cells During HBV-related Acute-on-chronic Liver Failure. World J Gastroenterol. 2014 Jul 14;20(26):8558-71. PubMed PMID: 25024610.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Changes in circulating Foxp3(+) regulatory T cells and interleukin-17-producing T helper cells during HBV-related acute-on-chronic liver failure. AU - Liang,Xue-Song, AU - Li,Cheng-Zhong, AU - Zhou,Yin, AU - Yin,Wei, AU - Liu,Ya-Yun, AU - Fan,Wen-Han, PY - 2013/10/15/received PY - 2013/12/31/revised PY - 2014/04/08/accepted PY - 2014/7/16/entrez PY - 2014/7/16/pubmed PY - 2015/4/14/medline KW - Hepatitis B virus KW - Hepatitis B virus-related acute-on-chronic liver failure KW - Immune KW - Th17 KW - Treg SP - 8558 EP - 71 JF - World journal of gastroenterology JO - World J. Gastroenterol. VL - 20 IS - 26 N2 - AIM: To longitudinally investigate cytokine gene expression and protein levels in Th17 and Treg cells, to observe T-cell phenotypes during hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACHBLF) and to analyze changes in Th17 and Treg phenotypes during disease progression. METHODS: We measured the expression of seven Th17/Treg differentiation-related genes and serum concentrations of the corresponding cytokines in 18 ACHBLF, 18 chronic hepatitis B (CHB) disease controls and 10 healthy controls (HCs) by real-time quantitative PCR and enzyme linked immunosorbent assay. Peripheral Th17 and Treg cell frequencies were analyzed by flow cytometry. RESULTS: From the onset of ACHBLF, patients presented with a conductive Th17 differentiation cytokine environment accompanied by high Th17 frequency and high serum IL-17 levels, which were sustained throughout the disease course. The Treg-related cytokine IL-2 and Foxp3 were also up-regulated from disease onset, and Foxp3 gene expression showed a gradually increasing trend during ACHBLF. The circular phenotype of Treg and Th17 cells showed changes from the onset of ACHGLF. At disease onset, Th17 frequency increased significantly compared with both CHB and HCs, but Treg cell frequency decreased significantly compared with CHB. During the ACHBLF event, Th17 frequency remained higher compared with HCs, but decreased sharply from the peak point to the recovery point; Treg cell frequency increased gradually during the ACHBLF event. Treg and Th17 cell counts correlated with ACHBLF development; in all patients, serum IL-17 levels significantly correlated with patient serum ALT levels. In survivors, Th17 frequency at the onset point and the Treg to Th17 ratio at the peak point correlated with the patient's model for end stage liver disease (MELD) plus sodium (MELD-Na) score. The Treg to Th17 ratio and the Th17 frequency at onset were significant predictors of patient survival. Low Treg/Th17 cell ratios at the onset predicted poor survival. Survivors exhibited an initial decrease in the circulating Treg/Th17 ratio from the onset to the peak time, and subsequently displayed a continuous increase. CONCLUSION: Treg and Th17 cells showed changes in genes, protein levels and T cell phenotypes during ACHBLF events. An increased Treg/Th17 ratio was associated with the survival of ACHBLF patients. SN - 2219-2840 UR - https://www.unboundmedicine.com/medline/citation/25024610/Changes_in_circulating_Foxp3_+__regulatory_T_cells_and_interleukin_17_producing_T_helper_cells_during_HBV_related_acute_on_chronic_liver_failure_ L2 - http://www.wjgnet.com/1007-9327/full/v20/i26/8558.htm DB - PRIME DP - Unbound Medicine ER -