Transcriptional Network Analysis Implicates Altered Hepatic Immune Function in NASH development and resolution.
Journal
Nature metabolism
ISSN: 2522-5812
Titre abrégé: Nat Metab
Pays: Germany
ID NLM: 101736592
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
entrez:
9
11
2019
pubmed:
9
11
2019
medline:
9
11
2019
Statut:
ppublish
Résumé
Progression of fatty liver to non-alcoholic steatohepatitis (NASH) is a rapidly growing health problem. Presence of inflammatory infiltrates in the liver and hepatocyte damage distinguish NASH from simple steatosis. However, the underlying molecular mechanisms involved in the development of NASH remain to be fully understood. Here we perform transcriptional and immune profiling of NASH patients before and after lifestyle intervention (LSI). Analysis of liver microarray data from a cohort of patients with histologically assessed NAFLD reveals a hepatic gene signature, which is associated with NASH and is sensitive to regression of NASH activity upon LSI independently of body weight loss. Enrichment analysis reveals the presence of immune-associated genes linked to inflammatory responses, antigen presentation and cytotoxic cells in the NASH-linked gene signature. In an independent cohort, NASH is also associated with alterations in blood immune cell populations, including conventional dendritic cells (cDC) type 1 and 2, and cytotoxic CD8 T cells. Lobular inflammation and ballooning are associated with the accumulation of CD8 T cells in the liver. Progression from simple steatosis to NASH in a mouse model of diet-driven NASH results in a comparable immune-related hepatic expression signature and the accumulation of intra-hepatic cDC and CD8 T cells. These results show that NASH, compared to normal liver or simple steatosis, is associated with a distinct hepatic immune-related gene signature, elevated hepatic CD8 T cells, and altered antigen-presenting and cytotoxic cells in blood. These findings expand our understanding of NASH and may identify potential targets for NASH therapy.
Identifiants
pubmed: 31701087
doi: 10.1038/s42255-019-0076-1
pmc: PMC6837876
mid: EMS84438
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Pagination
604-614Subventions
Organisme : European Research Council
ID : 694717
Pays : International
Commentaires et corrections
Type : ErratumIn
Déclaration de conflit d'intérêts
Competing interests: BS and SF are consultants for Genfit S.A. SF and LV are consultants for Inventiva. All other authors have nothing to declare.
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