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18 August 2019 : Clinical Research  

Foxp3⁺ Treg Cells Are Associated with Pathological Process of Autoimmune Hepatitis by Activating Methylation Modification in Autoimmune Hepatitis Patients

Jiang Chen1BCDEF, Wen Liu1BCDF, Wenjing Zhu2BF

DOI: 10.12659/MSM.915408

Med Sci Monit 2019; 25:6204-6212

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 AND 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.

Keywords: Autoimmune Diseases, Hepatitis, Methylation, T-Lymphocytes, Regulatory, Cytokines, DNA Methylation, Forkhead Transcription Factors, Hepatitis, Autoimmune, Liver, Liver Function Tests

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750