Roles of innate lymphoid cells in metabolic and alcohol-associated liver diseases

Abstract

Innate lymphoid cells (ILCs) have been identified as potent regulators of inflammation, cell death and wound healing, which are the main biological processes involved in the progression of chronic liver disease. Obesity and chronic alcohol consumption are the leading contributors to chronic liver diseases in developed countries, due to inappropriate lifestyles. In particular, inflammation is a key factor in these liver abnormalities and promotes the development of more severe lesions such as fibrosis, cirrhosis and hepatocellular carcinoma. Opposite roles of ILC subsets have been described in the development of chronic liver disease, depending on the stage and aetiology of the disease. The heterogeneous family of ILCs encompasses cytotoxic natural killer cells, the cytokine-producing type 1, 2 and 3 ILCs and lymphoid tissue inducer cells. Dysfunction of these immune cells provokes uncontrolled inflammation and tissue damage, which are the basis for tumour development. In this review, we provide an overview of the recent and putative roles of ILC subsets in obesity and alcohol-associated liver diseases, which are currently the major contributors to end-stage liver complications such as fibrosis/cirrhosis and hepatocellular carcinoma.

Keywords: ALD; MASLD; fibrosis; hepatocellular carcinoma; innate lymphoid cells.

Fig. 1

Major contributions of ILC subsets to immunity. Historically described roles and the main recently discovered contributions of ILCs to immune responses are described. ILC(s), innate lymphoid cell(s); ILC1-3, type 1-3 ILC(s); MASH, metabolic dysfunction-associated steatohepatitis; MASLD, metabolic dysfunction-associated steatotic liver disease; NK, natural killer.

Fig. 2

Roles of ILC subsets in chronic liver diseases. ILC involvement in the development of: liver abnormalities after high-caloric (top left) or excessive/chronic alcohol consumption (top right); fibrosis (middle); and HCC (bottom). ALD, alcohol-related liver disease; ASH, alcohol-related steatohepatitis; AT, adipose tissue; HCC, hepatocellular carcinoma; ILC(s), innate lymphoid cell(s); ILC1-3, type 1-3 ILC(s); MASH, metabolic dysfunction-associated steatohepatitis; MASLD, metabolic dysfunction-associated steatotic liver disease; NK, natural killer.