Defining the liver ILC2-stromal cell interactions and their regulatory impact on liver fibrosis.

Virtually all chronic liver diseases are associated with hepatic fibrosis and due to the world-wide epidemics of obesity the rapidly growing prevalence of metabolic induced non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) is a great cause for concern.

Hepatic fibrosis progression eventually leads to cirrhosis, liver failure and an increased risk of developing hepatocellular carcinoma where liver transplantation is the only treatment option.An extensive network of cells contribute to the development of hepatic fibrosis and elucidating their, yet poorly understood, crosstalk is an essential part to understanding the pathology of fibrogenesis.

Our preliminary data show that type 2 innate lymphoid cells (ILC2s) accumulate and localize in close proximity to stromal cells during hepatic fibrosis and share the perivascular niche with type 3 lymphocytes (T3Ls).

Our data also suggests that ILC2s have a regulatory role in hepatic fibrosis development.We hypothesize that liver fibrosis is regulated by niche interactions between ILC2s, T3Ls, and stromal cell subsets within the liver fibrotic niches.

In this project we will investigate the functional impact of these cellular subsets on one another and on the development of hepatic fibrosis.

Elucidating these cellular interactions will further the fundamental understanding of fibrosis pathogenesis and provide opportunities to identify key mechanistic pathways for therapeutic intervention.