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 used...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Korean Association for the Study of the Liver
2023-04-01
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| Series: | Clinical and Molecular Hepatology |
| Subjects: | |
| Online Access: | http://e-cmh.org/upload/pdf/cmh-2022-0205.pdf |
| _version_ | 1797844891304198144 |
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| author | Kathryn Jane Waller Hajar Saihi Wenhao Li James Hallimond Brindley Anja De Jong Wing-kin Syn Conrad Bessant William Alazawi |
| author_facet | Kathryn Jane Waller Hajar Saihi Wenhao Li James Hallimond Brindley Anja De Jong Wing-kin Syn Conrad Bessant William Alazawi |
| author_sort | Kathryn Jane Waller |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-09T17:29:41Z |
| format | Article |
| id | doaj.art-c8a158e68d7e4092842e8e454a51150f |
| institution | Directory Open Access Journal |
| issn | 2287-2728 2287-285X |
| language | English |
| last_indexed | 2024-04-09T17:29:41Z |
| publishDate | 2023-04-01 |
| publisher | Korean Association for the Study of the Liver |
| record_format | Article |
| series | Clinical and Molecular Hepatology |
| spelling | doaj.art-c8a158e68d7e4092842e8e454a51150f2023-04-18T07:21:34ZengKorean Association for the Study of the LiverClinical and Molecular Hepatology2287-27282287-285X2023-04-0129241743210.3350/cmh.2022.02051772Single-cell phenotypes of peripheral blood immune cells in early and late stages of non-alcoholic fatty liver diseaseKathryn Jane Waller0Hajar Saihi1Wenhao Li2James Hallimond Brindley3Anja De Jong4Wing-kin Syn5Conrad Bessant6William Alazawi7 Barts Liver Centre, Blizard Institute, Queen Mary University of London, London, UK Barts Liver Centre, Blizard Institute, Queen Mary University of London, London, UK Barts Liver Centre, Blizard Institute, Queen Mary University of London, London, UK Barts Liver Centre, Blizard Institute, Queen Mary University of London, London, UK Barts Liver Centre, Blizard Institute, Queen Mary University of London, London, UK Division of Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, SC, USA Centre for Computational Biology, Life Sciences Initiative, Queen Mary University of London, London, UK Barts Liver Centre, Blizard Institute, Queen Mary University of London, London, UKBackground/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.http://e-cmh.org/upload/pdf/cmh-2022-0205.pdfnafldmass cytometry |
| spellingShingle | Kathryn Jane Waller Hajar Saihi Wenhao Li James Hallimond Brindley Anja De Jong Wing-kin Syn Conrad Bessant William Alazawi Single-cell phenotypes of peripheral blood immune cells in early and late stages of non-alcoholic fatty liver disease Clinical and Molecular Hepatology nafld mass cytometry |
| 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 | nafld mass cytometry |
| url | http://e-cmh.org/upload/pdf/cmh-2022-0205.pdf |
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