https://scholars.lib.ntu.edu.tw/handle/123456789/640696
標題: | IL-21, not IL-17A, exacerbates murine primary biliary cholangitis | 作者: | Chan, Chun-Wen Chen, Hung-Wen Wang, Yu-Wen Lin, Chia-I YA-HUI CHUANG |
關鍵字: | Th17; autoimmune disease; interleukin-17A; interleukin-17F; interleukin-21; tissue-resident memory T cell | 公開日期: | 7-二月-2024 | 卷: | 215 | 期: | 2 | 來源出版物: | Clinical and experimental immunology | 摘要: | Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease caused by intrahepatic bile duct injuries, resulting in fibrosis, cirrhosis, and eventually liver failure. T helper (Th) 17 cells are proposed to involve in the pathogenesis of PBC. However, how and which Th17 cell-derived cytokines affect PBC remains unclear. In this study, we investigated the effects of Th17 effector cytokines, including interleukin (IL)-17A, IL-17F, and IL-21 in PBC using a xenobiotic-induced mouse model of autoimmune cholangitis (inducible chemical xenobiotic models of PBC) treated with cytokine-expressing adeno-associated virus. Our results showed that administration of IL-17A, the well-known main cytokine produced by Th17 cells, did not augment liver inflammation or fibrosis. In contrast, we noted IL-17A-treated mice had lower hepatic Th1 cell numbers and higher hepatic CD11b+Ly6G+ polymorphonuclear myeloid-derived suppressor cell numbers. IL-17F did not alter liver inflammation or fibrosis. However, the administration of IL-21 exacerbated liver inflammatory responses and portal cell infiltration. IL-21 markedly increased the numbers of activated CD8+ T cells and liver tissue-resident memory CD8+ T cells. Moreover, IL-21 aggravates liver fibrosis in mice with autoimmune cholangitis. These results emphasized that not IL-17A but IL-21 in Th17 cell-derived cytokines affected the pathogenesis of PBC. IL-21 enhanced liver inflammation and progression to fibrosis by enhancing the numbers and effector activities of CD8+ T cells. Delineation of the effects of different Th17 effector cytokines in PBC offers clues for developing new therapeutic approaches. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/640696 | ISSN: | 00099104 | DOI: | 10.1093/cei/uxad107 |
顯示於: | 醫學檢驗暨生物技術學系 |
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