Emperipolesis mediated by CD8⁺ T cells correlates with biliary epithelia cell injury in primary biliary cholangitis

Abstract

Primary biliary cholangitis (PBC) is an autoimmune disease characterized by chronic destruction of the bile ducts. A major unanswered question regarding the pathogenesis of PBC is the precise mechanisms of small bile duct injury. Emperipolesis is one of cell‐in‐cell structures that is a potential histological hallmark associated with chronic hepatitis B. This study aimed to clarify the pathogenesis and characteristics of emperipolesis in PBC liver injury. Sixty‐six PBC patients, diagnosed by liver biopsy combined with laboratory test, were divided into early‐stage PBC (stages I and II, n = 39) and late‐stage PBC (stages III and IV, n = 27). Emperipolesis was measured in liver sections stained with haematoxylin‐eosin. The expressions of CK19, CD3, CD4, CD8, CD20, Ki67 and apoptosis of BECs were evaluated by immunohistochemistry or immunofluorescence double labelling. Emperipolesis was observed in 62.1% of patients with PBC, and BECs were predominantly host cells. The number of infiltrating CD3+ and CD8+ T cells correlated with the advancement of emperipolesis (R2 = 0.318, P < .001; R2 = 0.060, P < .05). The cell numbers of TUNEL‐positive BECs and double staining for CK19 and Ki67 showed a significant positive correlation with emperipolesis degree (R2 = 0.236, P < .001; R2 = 0.267, P < .001). We conclude that emperipolesis mediated by CD8+ T cells appears to be relevant to apoptosis of BEC and thus may aggravate the further injury of interlobular bile ducts.

Serotonin: A Potent Immune Cell Modulator in Autoimmune Diseases

“…In the early stage of PBC, NK cell killing activity is enhanced, and monocytes and macrophages have a high response to pathogen-associated antigens (66). Then, Th1 cells and cytotoxic T lymphocyte are activated (67,68). Furthermore, autoreactive B cells secrete large amount of antimitochondrial antibodies (69).…”

CD8+ T cells actively penetrate hepatocytes via the CD44/p‐ERM/F‐actin pathway in autoimmune hepatitis

“…Compared with the control group, the cell-in-cell structure in the liver tissue of these two models significantly increased. 5 Moreover, emperipolesis also increased in chronic viral infection, 16 PBC 17 and DILI. 18 These studies suggest that emperipolesis appears during liver inflammation, and may play a role in liver injury or T cell clearance.…”

The Proinflammatory Cytokines IL-18, IL-21, and IFN-γ Differentially Regulate Liver Inflammation and Anti-Mitochondrial Antibody Level in a Murine Model of Primary Biliary Cholangitis

“…The contribution of AMA in PBC onset and progression is still unclear even though it has been a key clinical diagnostic indicator of PBC. Based on liver biopsies of PBC patients, CD4 + T, CD8 + T, and B cells were infiltrated in the inflammatory foci [ 27 , 28 ]. Their roles during the onset and progression of PBC still remain unknown.…”