| Summary: | 碩士 === 國立臺灣大學 === 醫學檢驗暨生物技術學研究所 === 105 === Primary biliary cholangitis (PBC) is an autoimmune liver disease. Previous study showed that serum interleukin (IL)-21 is highly expressed in early diagnosed PBC patients. IL-21 is a member of IL-2 family which has been reported to be a pleiotropic cytokine that mediates numerous cell types. However, the mechanism of IL-21 in PBC remains unclear. In this study, we used a mouse model of PBC to evaluate the roles of IL-21 in autoimmune liver inflammation. Mice were immunized with 2-octynoic acid-OVA mixed with complete/incomplete Freund’s adjuvant biweekly through i.p. to form PBC. Adeno-associated virus (AAV)-mIL-21 was given at week 1 by i.v. to express mIL-21 in liver. Mice were euthanized to examine the differences among groups. Antimitochondrial antibody (AMA) against pyruvate dehydrogenase E2 complex (PDC-E2), a specific hallmark of PBC, was detected in all groups. The numbers of liver mononuclear cells (LMNCs), mRNA expression level of proinflammatory cytokine IFN-γ increased in AAV-mIL-21 injected group. In addition, the percentage of T, CD8+ T, follicular helper T (Tfh) cells increased with the existence of mIL-21. Furthermore, CD8+ T cells were highly activated and granzyme B were further upregulated in early-stage PBC. Moreover, the histopathology sections stained by Masson’s trichrome stain showed exacerbated liver fibrosis in AAV-mIL-21 injected group and mRNA expression levels of collagen III revealed the data. The results indicate that IL-21 may exacerbate PBC by upregulating CD8+ T cells and further enhance liver fibrosis.
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