Increased interleukin-23 receptor (IL-23R) expression is associated with disease severity in acute-on-chronic liver failure.
Acute-On-Chronic Liver Failure
/ blood
Adult
Case-Control Studies
Cytokines
/ blood
Female
Gene Expression Regulation
/ immunology
Hepatitis B, Chronic
/ blood
Humans
India
Liver
/ pathology
Male
Middle Aged
Receptors, Interleukin
/ blood
Severity of Illness Index
Th17 Cells
/ immunology
Young Adult
IL-17A
IL-23R
alcoholic hepatitis
cirrhosis
hepatitis B
liver failure
Journal
Liver international : official journal of the International Association for the Study of the Liver
ISSN: 1478-3231
Titre abrégé: Liver Int
Pays: United States
ID NLM: 101160857
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
15
02
2018
revised:
22
08
2018
accepted:
17
11
2018
pubmed:
7
12
2018
medline:
22
9
2020
entrez:
4
12
2018
Statut:
ppublish
Résumé
Th17 cells mediated immune response is important in chronic hepatitis B (CHB) infection and inflammation associated diseases; however, little is known about their immunopathogenic role in acute-on-chronic liver failure (ACLF). Interleukin-23 receptor (IL-23R) is essential for the generation of pathogenic Th17 cells; therefore, we aimed to evaluate IL-23R expression and its correlation with disease severity in ACLF. Forty-two patients with ACLF (HBV and alcohol-related), thirty-two with CHB and twenty healthy controls (HC) were studied. Circulating and intrahepatic profile of Th17 cells and IL-23R was investigated. Association of IL-23R with disease severity was determined. Circulating Th17 cells were significantly increased in both ACLF groups (P = 0.03, P = 0.006) than CHB and HC. Percentage of Th17 cells was higher in liver than peripheral blood of ACLF patients (P = 0.04). Expression of IL-23R was immensely up-regulated on Th17 cells of ACLF patients. Importantly, IL-23R not only correlated with the increased percentage of Th17 cells but also had significant association with inflammation (P = 0.03) and clinical disease severity indices including Child-Turcotte-Pugh (P = 0.001) and Model for End-Stage Liver Disease (P = 0.002) scores. The ACLF non-survivors showed higher IL-23R expression (P = 0.01). Transcription factor retinoic acid receptor-related orphan nuclear receptor gamma-t (ROR-γt) was also high in circulation and in liver of ACLF patients and it positively correlated with ALT levels (P = 0.03). Surface receptors, including CCR6, IL-17R and pro-inflammatory cytokines IL-17A, IL-22, CXCL8 and GM-CSF were highly augmented in ACLF. ACLF patients express high IL-23R on Th17 cells which induces inflammation and strongly correlates with liver disease severity.
Sections du résumé
BACKGROUND
Th17 cells mediated immune response is important in chronic hepatitis B (CHB) infection and inflammation associated diseases; however, little is known about their immunopathogenic role in acute-on-chronic liver failure (ACLF). Interleukin-23 receptor (IL-23R) is essential for the generation of pathogenic Th17 cells; therefore, we aimed to evaluate IL-23R expression and its correlation with disease severity in ACLF.
METHODS
Forty-two patients with ACLF (HBV and alcohol-related), thirty-two with CHB and twenty healthy controls (HC) were studied. Circulating and intrahepatic profile of Th17 cells and IL-23R was investigated. Association of IL-23R with disease severity was determined.
RESULTS
Circulating Th17 cells were significantly increased in both ACLF groups (P = 0.03, P = 0.006) than CHB and HC. Percentage of Th17 cells was higher in liver than peripheral blood of ACLF patients (P = 0.04). Expression of IL-23R was immensely up-regulated on Th17 cells of ACLF patients. Importantly, IL-23R not only correlated with the increased percentage of Th17 cells but also had significant association with inflammation (P = 0.03) and clinical disease severity indices including Child-Turcotte-Pugh (P = 0.001) and Model for End-Stage Liver Disease (P = 0.002) scores. The ACLF non-survivors showed higher IL-23R expression (P = 0.01). Transcription factor retinoic acid receptor-related orphan nuclear receptor gamma-t (ROR-γt) was also high in circulation and in liver of ACLF patients and it positively correlated with ALT levels (P = 0.03). Surface receptors, including CCR6, IL-17R and pro-inflammatory cytokines IL-17A, IL-22, CXCL8 and GM-CSF were highly augmented in ACLF.
CONCLUSION
ACLF patients express high IL-23R on Th17 cells which induces inflammation and strongly correlates with liver disease severity.
Substances chimiques
Cytokines
0
IL23R protein, human
0
Receptors, Interleukin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1062-1070Informations de copyright
© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.