Gastrointestinal B-cells license metabolic T-cell activation in NASH microbiota anigen-independently and contribute to fibrosis by IgA-FcRy signalling

ABSTRACT: Non-alcoholic steatohepatitis (NASH) is a T-cell mediated, auto-aggressive condition that can result in progressive liver disease and hepatocellular carcinoma. Gastrointestinal B-cells are activated and increased in number in mouse and human NASH, licensing metabolic-cell activation to induce NASH antigen- and microbiota-independently. Genetic or therapeutic depletion of B-cells systemically or gastrointestinal B-cells specifically prevented or reverted NASH and fibrosis. Clinical and molecular analyses from NASH patients demonstrated IgA-levels and activated FcRy+ hepatic myeloid cells to correlate with liver fibrosis degree.

ORGANISM(S): Homo sapiens

PROVIDER: GSE190487 | GEO | 2022/02/01

REPOSITORIES: GEO