| Background and Aims T-helper (Th) 22 is involved in the pathogenesis of hepatitis B virus (HBV)-associated liver damage. However, little is known regarding the immunopathogenic role of liver fibrosis in patients with HBV-associated liver fibrosis. So we aimed to reveal the cell expression and the significance of Th22 in the development of chronic hepatitis B and liver cirrhosis.Methods Thirty six patients with HBV-associated liver cirrhosis (LC), twenty one patients with chronic hepatitis B (CHB) and twenty healthy controls (HC) were enrolled. Flow cytometry was employed to determine the Th22 frequency in peripheral blood. Plasma interleukin-22(IL-22) levels were measured by enzyme linked immunosorbent assay (ELISA). The expressions of IL-22 messenger RNA (mRNA)、IL-22R1 mRNA、AHR mRNA、TNF-α mRNA、RORC mRNA and IL-6 mRNA in liver tissues were examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR).HE and Masson staining were used to observe the liver tissue pathological changes and the grading degree of liver inflammation and fibrosis was according to the Scheuer eriteria. The expression of IL-22 in liver tissue was peformed by immunohistochemical staining. Related serological and virology indicators were detected by automatic biochemistry analyzer.Results 1. Peripheral blood of Th22 frequencies in LC group were significantly increased compared with CHB group and HC group, comparative differences between groups were statistically significant (P<0.001).2.The levels of plasma IL-22 in LC group were significantly higher than that in CHB group and HC group, comparative differences between groups were also statistically significant(P<0.001).3. Correlation analysis showed that the concentration of plasma IL-22 significantly correlated with the frequency of Th22 cells in peripheral blood within LC patients (r=0.603, P=0.000) and CHB patients(r=0.486, P=0.025).4. The gene expression of IL-22 mRNA、IL-22R1 mRNA、AHR mRNA、RORC mRNA、IL-6 mRNA in liver tissue of LC group were all significantly higher than that in HC group, comparative differences between groups were statistically significant(P<0.05); but the expression of TNF-α mRNA were lower than that in HC group, and the results did not prompt that the difference was statistically significant(P>0.05).5. HE staining showed that in liver tissue of LC group, normal hepatic lobular architecture was damaged, and replaced by false lobule, a large number of inflammatory cells and fibroblasts was observed in fibrous septum. Masson’s staining showed that a large number of collagen fibers deposition in portal area or beside the central vein, Fibrous tissue segmentation normal hepatic lobular to form false lobule. In HC group, HE and Masson’s staining both show normal hepatic lobular architecture, and there was no fibrous tissue segmentation.6. Immunohistochemical analysis of IL-22 staining shows that little or no IL-22+ lymphocytes was fund in HC group, however, in LC group, most of the IL-22+ lymphocytes were concentrated in the portal area and hepatic sinusoids, especially in the portal area. Increased IL-22-positive staining was observed in livers of cirrhotic patients compared with healthy controls, the difference was statistically significant(P<0.001). In LC group, positively correlation was found between the number of IL-22+ cells and the degree of hepatic inflammation or the stage of hepatic fibrosis.Conclusion 1. High expression of Th22 cells and its cytokine IL-22、 transcription factors, other cytokines which positively correlated with the degree of hepatic inflammation and the stage of hepatic fibrosis, prompting that Th22 cells is an important inflammatory cells.2. Th22 cells play an important role in the process of chronic hepatitis B and cirrhosis, and may be used as a testing index of disease severity and prognosis.3. Further research for Th22 cells and its main effector cytokines will provide new ideas for clinical decision making. |
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