Imaging and immunometabolic phenotyping uncover changes in the hepatic immune response in the early phases of NAFLD
Carregando...
Data
Título da Revista
ISSN da Revista
Título de Volume
Editor
Universidade Federal de Minas Gerais
Descrição
Tipo
Artigo de periódico
Título alternativo
A imagem e a fenotipagem imunometabólica revelam alterações na resposta imune hepática nas fases iniciais da NAFLD
Primeiro orientador
Membros da banca
Resumo
Background & Aims: The precise determination of non-alcoholic fatty liver disease (NAFLD) onset is challenging. Thus, the
initial hepatic responses to fat accumulation, which may be fundamental to our understanding of NAFLD evolution and
clinical outcomes, are largely unknown. Herein, we chronologically mapped the immunologic and metabolic changes in the
liver during the early stages of fatty liver disease in mice and compared this with human NAFLD samples.
Methods: Liver biopsies from patients with NAFLD (NAFLD activity score [NAS] 2–3) were collected for gene expression
profiling. Mice received a high-fat diet for short periods to mimic initial steatosis and the hepatic immune response was
investigated using a combination of confocal intravital imaging, gene expression, cell isolation, flow cytometry and bone
marrow transplantation assays. Results: We observed major immunologic changes in patients with NAS 2–3 and in mice in the initial stages of NAFLD. In mice, these changes significantly increased mortality rates upon drug-induced liver injury, as well as predisposing mice to bacterial infections. Moreover, deletion of Toll-like receptor 4 in liver cells dampened tolerogenesis, particularly in Kupffer
cells, in the initial stages of dietary insult. Conclusion: The hepatic immune system acts as a sentinel for early and minor changes in hepatic lipid content, mounting a biphasic response upon dietary insult. Priming of liver immune cells by gut-derived Toll-like receptor 4 ligands plays an important role in liver tolerance in initial phases, but continuous exposure to insults may lead to damage and reduced ability to control infections.
Abstract
Assunto
Hepatopatia gordurosa não alcoólica, Fígado, Sistema Imunitário, Dieta, Metabolismo, Imunidade
Palavras-chave
NAFLD, Liver, Steatosis, Immune system, Diet, Metabolism, In vivo imaging, Immunity
Citação
Curso
Endereço externo
https://www.sciencedirect.com/science/article/pii/S2589555920300513?via%3Dihub