Objectives: Autoimmune hepatitis (AIH) is an aberrant autoimmune condition mediated by T cell abnormality, which may cause fulminant liver failure and persistent liver injury. This study aimed to disclose the histopathological and functional engagement of interleukin (IL)-26, a potent inflammation mediator, in AIH disease progression.
Methods: We conducted immunohistochemical staining on liver biopsy samples to evaluate intrahepatic expression of IL-26. Cellular sources of hepatic IL-26 were detected by confocal microscopy. Flow cytometry was employed to determine the immunological alterations of CD4+ and CD8+ T cells following in vitro IL-26 treatment on primary peripheral blood mononuclear cells from healthy controls.
Results: Statistically significant increase in IL-26 level was observed in AIH (n = 48) liver samples in comparison with patients having chronic hepatitis B (n = 25), nonalcoholic fatty liver disease (n = 18), and healthy donors for living donor liver transplantation (n = 10). The number of intrahepatic IL-26+ cells was positively correlated with histological and serological severity. An immunofluorescence staining indicated that liver-infiltrating CD4+ T cells, CD8+ T cells, and CD68+ macrophages orchestrated IL-26 secretion in AIH. Both CD4+ and CD8+ T cells demonstrated effective activation, lytic, and proinflammatory functions upon IL-26 stimulation.
Conclusion: We observed elevated IL-26 in AIH liver which promoted T cell activation and cytotoxic capacity, indicating a therapeutic potential of IL-26 intervention in AIH.
Keywords: autoimmune hepatitis; cytotoxicity; interleukin-26; proinflammatory.
© 2023 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.