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Single-cell phenotypes of peripheral blood immune cells in early and late stages of non-alcoholic fatty liver disease

BACKGROUND/AIMS: Immune and inflammatory cells respond to multiple pathological hits in the development of nonalcoholic steatohepatitis (NASH) and fibrosis. Relatively little is known about how their type and function change through the non-alcoholic fatty liver disease (NAFLD) spectrum. Here we use...

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Autores principales: Waller, Kathryn Jane, Saihi, Hajar, Li, Wenhao, Brindley, James Hallimond, De Jong, Anja, Syn, Wing-kin, Bessant, Conrad, Alazawi, William
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Association for the Study of the Liver 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10121278/
https://www.ncbi.nlm.nih.gov/pubmed/36727210
http://dx.doi.org/10.3350/cmh.2022.0205
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author Waller, Kathryn Jane
Saihi, Hajar
Li, Wenhao
Brindley, James Hallimond
De Jong, Anja
Syn, Wing-kin
Bessant, Conrad
Alazawi, William
author_facet Waller, Kathryn Jane
Saihi, Hajar
Li, Wenhao
Brindley, James Hallimond
De Jong, Anja
Syn, Wing-kin
Bessant, Conrad
Alazawi, William
author_sort Waller, Kathryn Jane
collection PubMed
description BACKGROUND/AIMS: Immune and inflammatory cells respond to multiple pathological hits in the development of nonalcoholic steatohepatitis (NASH) and fibrosis. Relatively little is known about how their type and function change through the non-alcoholic fatty liver disease (NAFLD) spectrum. Here we used multi-dimensional mass cytometry and a tailored bioinformatic approach to study circulating immune cells sampled from healthy individuals and people with NAFLD. METHODS: Cytometry by time of flight using 36 metal-conjugated antibodies was applied to peripheral blood mononuclear cells (PBMCs) from biopsy-proven NASH fibrosis (late disease), steatosis (early disease), and healthy patients. Supervised and unsupervised analyses were used, findings confirmed, and mechanisms assessed using independent healthy and disease PBMC samples. RESULTS: Of 36 PBMC clusters, 21 changed between controls and disease samples. Significant differences were observed between diseases stages with changes in T cells and myeloid cells throughout disease and B cell changes in late stages. Semi-supervised gating and re-clustering showed that disease stages were associated with fewer monocytes with active signalling and more inactive NK cells; B and T cells bearing activation markers were reduced in late stages, while B cells bearing co-stimulatory molecules were increased. Functionally, disease states were associated with fewer activated mucosal-associated invariant T cells and reduced toll-like receptor-mediated cytokine production in late disease. CONCLUSIONS: A range of innate and adaptive immune changes begin early in NAFLD, and disease stages are associated with a functionally less active phenotype compared to controls. Further study of the immune response in NAFLD spectrum may give insight into mechanisms of disease with potential clinical application.
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spelling pubmed-101212782023-04-22 Single-cell phenotypes of peripheral blood immune cells in early and late stages of non-alcoholic fatty liver disease Waller, Kathryn Jane Saihi, Hajar Li, Wenhao Brindley, James Hallimond De Jong, Anja Syn, Wing-kin Bessant, Conrad Alazawi, William Clin Mol Hepatol Original Article BACKGROUND/AIMS: Immune and inflammatory cells respond to multiple pathological hits in the development of nonalcoholic steatohepatitis (NASH) and fibrosis. Relatively little is known about how their type and function change through the non-alcoholic fatty liver disease (NAFLD) spectrum. Here we used multi-dimensional mass cytometry and a tailored bioinformatic approach to study circulating immune cells sampled from healthy individuals and people with NAFLD. METHODS: Cytometry by time of flight using 36 metal-conjugated antibodies was applied to peripheral blood mononuclear cells (PBMCs) from biopsy-proven NASH fibrosis (late disease), steatosis (early disease), and healthy patients. Supervised and unsupervised analyses were used, findings confirmed, and mechanisms assessed using independent healthy and disease PBMC samples. RESULTS: Of 36 PBMC clusters, 21 changed between controls and disease samples. Significant differences were observed between diseases stages with changes in T cells and myeloid cells throughout disease and B cell changes in late stages. Semi-supervised gating and re-clustering showed that disease stages were associated with fewer monocytes with active signalling and more inactive NK cells; B and T cells bearing activation markers were reduced in late stages, while B cells bearing co-stimulatory molecules were increased. Functionally, disease states were associated with fewer activated mucosal-associated invariant T cells and reduced toll-like receptor-mediated cytokine production in late disease. CONCLUSIONS: A range of innate and adaptive immune changes begin early in NAFLD, and disease stages are associated with a functionally less active phenotype compared to controls. Further study of the immune response in NAFLD spectrum may give insight into mechanisms of disease with potential clinical application. The Korean Association for the Study of the Liver 2023-04 2022-11-21 /pmc/articles/PMC10121278/ /pubmed/36727210 http://dx.doi.org/10.3350/cmh.2022.0205 Text en Copyright © 2023 by The Korean Association for the Study of the Liver https://creativecommons.org/licenses/by-nc/3.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Waller, Kathryn Jane
Saihi, Hajar
Li, Wenhao
Brindley, James Hallimond
De Jong, Anja
Syn, Wing-kin
Bessant, Conrad
Alazawi, William
Single-cell phenotypes of peripheral blood immune cells in early and late stages of non-alcoholic fatty liver disease
title Single-cell phenotypes of peripheral blood immune cells in early and late stages of non-alcoholic fatty liver disease
title_full Single-cell phenotypes of peripheral blood immune cells in early and late stages of non-alcoholic fatty liver disease
title_fullStr Single-cell phenotypes of peripheral blood immune cells in early and late stages of non-alcoholic fatty liver disease
title_full_unstemmed Single-cell phenotypes of peripheral blood immune cells in early and late stages of non-alcoholic fatty liver disease
title_short Single-cell phenotypes of peripheral blood immune cells in early and late stages of non-alcoholic fatty liver disease
title_sort single-cell phenotypes of peripheral blood immune cells in early and late stages of non-alcoholic fatty liver disease
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10121278/
https://www.ncbi.nlm.nih.gov/pubmed/36727210
http://dx.doi.org/10.3350/cmh.2022.0205
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