Investigation of liver immune responses of males and females in the initiation of primary biliary cholangitis

碩士 === 國立臺灣大學 === 醫學檢驗暨生物技術學研究所 === 107 === Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease which caused by inflammation targeting intrahepatic small bile ducts. A sex disparity happens in PBC with a female-to-male ratio of 10:1. However, the reason why females outnumber male...

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Bibliographic Details
Main Authors: Chih-Yu Liu, 劉芝宇
Other Authors: Ya-Hui Chuang
Format: Others
Language:en_US
Published: 2019
Online Access:http://ndltd.ncl.edu.tw/handle/3ezxh2
Description
Summary:碩士 === 國立臺灣大學 === 醫學檢驗暨生物技術學研究所 === 107 === Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease which caused by inflammation targeting intrahepatic small bile ducts. A sex disparity happens in PBC with a female-to-male ratio of 10:1. However, the reason why females outnumber males remains unclear. In this study, we investigated whether the female-predominant effect of PBC results from female and male experience different immune responses in the initiation of PBC by using the xenobiotic-induced PBC murine model. Our results showed that the female PBC mice expressed more exacerbating liver inflammation and cell infiltration than the male PBC mice in the initiation of diseases. The percentage of liver CD8+ T cells was increased in female PBC mice, while effector CD4+ T cells and Foxp3+ regulatory cells were comparable. Although the two groups exhibited parallel functions of CD8+ T cells, CD4+ Teff expressed more activation and inhibition markers, and Foxp3+ Tregs expressed more suppression-maintaining markers in the male PBC mice.CXCL9 and CXCL10, which play crucial roles in trafficking infiltrating cells, expressed higher levels in the liver of female PBC mice. However, there were no differences between the chemokines receptor, CXCR3, between the two groups. In summary, our data indicated that the female mice exhibited more effector immune response might result from an imbalance of Teff/ Tregs in the initiation of PBC.