Investigating the effect of IL-17 on ductular reaction during liver regeneration

Ward, Eleanor (2022). Investigating the effect of IL-17 on ductular reaction during liver regeneration. University of Birmingham. M.Sc.

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Abstract

NAFLD is a highly prevalent disease, currently affecting an estimated 25% of the global population. Liver transplantation remains the only curative treatment, but this is becoming increasingly limited due to lack of donor availability, viable organs, organ rejection, and disease recurrence. Hepatic progenitor cells are activated following chronic liver damage, expanding to replace the liver’s hepatocyte and cholangiocyte population. This is accompanied by ductular reaction (DR), a compensatory mechanism involving the remodelling of bile ducts. In this investigation, we demonstrate a novel pathway involving IL-17A, a proinflammatory cytokine, which drives the bipotency of these progenitor cells to promote ductular reaction and liver regeneration by stimulating expression of the stem cell marker, CD133. This is achieved through various signalling pathways, most notably NF-κB and Wnt, factors of which are significantly upregulated following IL-17A treatment of cholangiocyte-derived hepatic progenitor cells (cdHPCs). FACS analysis revealed CD11b+ Ly6G+ neutrophils to be the major source of IL-17A in a mouse model of fatty liver disease. This study indicates that IL-17A may act as a potential therapeutic target to mediate cdHPC-driven liver regeneration, preventing the need for liver transplantation in the future.

Type of Work:

Thesis (Masters by Research > M.Sc.)

Award Type:

Masters by Research > M.Sc.

Supervisor(s):