IL‐26 modulates T cell function in autoimmune hepatitis

Abstract

ObjectivesAutoimmune 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.MethodsWe 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.ResultsStatistically 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.ConclusionWe 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.