Foxp3+ Treg cells are associated with pathological process of autoimmune hepatitis by activating methylation modification in autoimmune hepatitis patients

Abstract

Background: Autoimmune hepatitis (AIH) is a chronic hepatic disorder. This study investigated role of Foxp3+ regulatory T cells (Treg) and methylation-regulated Tregs in AIH pathological processes. Material/Methods: Forty consecutive patients diagnosed with hepatitis were enrolled and divided into a virus hepatitis (n=20) group and an AIH group (n=20). Twenty healthy individuals were assigned to the healthy control group (HC, n=20), Liver function biomarkers were detected on an automatic biochemical analyzer. Serum auto-antibodies were evaluated using immunofluorescence method. Histopathological evaluation was conducted with liver tissues. Treg cells were counted using FACS flow cytometry. Peripheral lymphocytes surface/intracellular biomarkers, CD4+CD25+, CD127, and Foxp3, were examined. Serum cytokines were evaluated using cytometric bead array. Methylation-specific PCR (MS-PCR) was conducted to identify the status of Foxp3 gene methylation. Results: Levels of liver function biomarkers were significantly increased in the AIH group compared to the HC group (p<0.05). Levels of ANA and ASMA were significantly enhanced in the AIH group compared to the HC group (p<0.05). Other auto-antibodies, including anti-AHA, anti-ribosome P protein, and anti-RO-52, were also discovered in the AIH group. Severe lymphocytic infiltration and inflammatory cells clustering were discovered in AIH patients. There were significantly fewer CD4+CD25+ T cells in the AIH group, and interleukin 6 (IL-6) and IL-10 levels were significantly decreased compared to the HC group (p<0.05). CD127+ Treg and Foxp3+ Treg expressions were decreased in the AIH group compared to the HC group (p<0.05). Foxp3 in Treg cells of AIH patients exhibited higher methylation frequency compared to that of HC patients (p<0.05). Conclusions: Foxp3+ regulatory T cells were involved in pathological processes by activating methylation modification in autoimmune hepatitis patients.