Interleukin-17-producing CD4(+) T cells increase with severity of liver damage in patients with chronic hepatitis B.
Interleukin-17 (IL-17)-producing CD4(+) T cells (Th17)-mediated immune response has been demonstrated to play a critical role in inflammation-associated disease; however, its role in chronic hepatitis B virus (HBV) infection remains unknown. Here we characterized peripheral and intrahepatic Th17 cells and analyzed their association with liver injury in a cohort of HBV-infected patients including 66 with chronic hepatitis B (CHB), 23 with HBV-associated acute-on-chronic liver failure (ACLF), and 30 healthy subjects as controls. The frequency of circulating Th17 cells increased with disease progression from CHB (mean, 4.34%) to ACLF (mean, 5.62%) patients versus healthy controls (mean, 2.42%). Th17 cells were also found to be largely accumulated in the livers of CHB patients. The increases in circulating and intrahepatic Th17 cells positively correlated with plasma viral load, serum alanine aminotransferase levels, and histological activity index. In vitro, IL-17 can promote the activation of myeloid dendritic cells and monocytes and enhance the capacity to produce proinflammatory cytokines IL-1beta, IL-6, tumor necrosis factor (TNF)-alpha, and IL-23 in both CHB patients and healthy subjects. In addition, the concentration of serum Th17-associated cytokines was also increased in CHB and ACLF patients.


CONCLUSIONS
Th17 cells are highly enriched in both peripheral blood and liver of CHB patients, and exhibit a potential to exacerbate liver damage during chronic HBV infection.
Zhang
Ji-Yuan
JY
Research Center for Biological Therapy, Beijing, China.
Zhang
Zheng
Z
Lin
Fang
F
Zou
Zheng-Sheng
ZS
Xu
Ruo-Nan
RN
Jin
Lei
L
Fu
Jun-Liang
JL
Shi
Feng
F
Shi
Ming
M
Wang
Hui-Fen
HF
Wang
Fu-Sheng
FS
D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology*; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D019694:Hepatitis B, Chronic / Q000276:immunology / Q000473:pathology*; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis*; D008099:Liver / Q000166:cytology / Q000276:immunology; D008297:Male; D008875:Middle Aged
D020381:Interleukin-17