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IL-21, not IL-17A, exacerbates murine primary biliary cholangitis
Chun-Wen Chan1, Hung-Wen Chen1, Yu-Wen Wang1
1Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Clinical and Experimental Immunology
|September 14, 2023
Summary
Interleukin-21 (IL-21), not IL-17A, exacerbates primary biliary cholangitis (PBC) by promoting liver inflammation and fibrosis through CD8+ T cell activation. This finding offers new therapeutic targets for autoimmune liver disease.
Area of Science:
- Immunology
- Hepatology
- Autoimmune Diseases
Background:
- Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease.
- T helper 17 (Th17) cells are implicated in PBC pathogenesis.
- The specific roles of Th17-derived cytokines in PBC are not fully understood.
Purpose of the Study:
- To investigate the effects of key Th17 effector cytokines (IL-17A, IL-17F, IL-21) on PBC pathogenesis.
- To elucidate the mechanisms by which these cytokines influence liver inflammation and fibrosis.
Main Methods:
- Utilized a xenobiotic-induced mouse model of autoimmune cholangitis.
- Administered cytokine-expressing adeno-associated viruses (IL-17A, IL-17F, IL-21).
- Analyzed hepatic immune cell populations and fibrosis markers.
Main Results:
- IL-17A and IL-17F did not augment liver inflammation or fibrosis.
- IL-21 administration exacerbated liver inflammation, portal cell infiltration, and fibrosis.
- IL-21 increased the numbers of activated CD8+ T cells and liver tissue-resident memory CD8+ T cells.
Conclusions:
- IL-21, a Th17-derived cytokine, significantly contributes to PBC pathogenesis.
- IL-21 promotes liver inflammation and fibrosis by enhancing CD8+ T cell responses.
- Targeting IL-21 may offer a novel therapeutic strategy for PBC.
