Immune Landscape Changes in MASLD and the Effects of 11β‐HSD1 Inhibition Revealed by Single‐Cell Mass Cytometry
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2025
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| author | Zayakhuu Gerelkhuu Sehee Park Yun Kim Sang Won Lee Dae Won Jun Tae Hyun Yoon |
| author_facet | Zayakhuu Gerelkhuu Sehee Park Yun Kim Sang Won Lee Dae Won Jun Tae Hyun Yoon Zayakhuu Gerelkhuu Sehee Park Yun Kim Sang Won Lee Dae Won Jun Tae Hyun Yoon |
| collection | Wiley Open Access |
| contents | Immune Landscape Changes in MASLD and the Effects of 11β‐HSD1 Inhibition Revealed by Single‐Cell Mass Cytometry Zayakhuu Gerelkhuu Sehee Park Yun Kim Sang Won Lee Dae Won Jun Tae Hyun Yoon PROTEOMICS – Clinical Applications ABSTRACTBackground: Metabolic dysfunction‐associated steatotic liver disease (MASLD) affects nearly one‐fourth of the global population, yet effective diagnostics and treatments remain limited. Systemic immune dysregulation plays a key role in MASLD pathogenesis, highlighting the value of immune profiling.Methods: In this study, we used high‐dimensional single‐cell mass cytometry (CyTOF) to analyze peripheral blood mononuclear cells (PBMCs) from healthy donors (n = 6), MASLD patients (n = 4), and MASLD patients treated with an 11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1) inhibitor (n = 2). PBMCs were stained with a 29‐marker panel to identify 15 immune cell types and assess cytokine expression.Results: MASLD patients showed increased CD8⁺ T cells, early NK cells, and monocytes, along with reductions in TH2, TH1, late NK, and Treg cells. Cytokine profiling revealed elevated IL‐6 expression in plasmacytoid dendritic cells and late NK cells, indicating systemic inflammation. Automated clustering (PhenoGraph, UMAP) identified NK and phagocytic subsets associated with disease and treatment. Notably, 11β‐HSD1 inhibition led to downregulation of pro‐inflammatory cytokines (e.g., IFN‐γ, IL‐6) and partial restoration of immune subsets.Conclusions: These results offer a high‐resolution view of immune alterations in MASLD and suggest that 11β‐HSD1 inhibition may represent a promising immunomodulatory therapeutic strategy. 10.1002/prca.70022 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| doi_str_mv | 10.1002/prca.70022 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_prca_70022 |
| institution | Wiley Open Access |
| license_str_mv | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| publishDate | 2025 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Immune Landscape Changes in MASLD and the Effects of 11β‐HSD1 Inhibition Revealed by Single‐Cell Mass Cytometry Zayakhuu Gerelkhuu Sehee Park Yun Kim Sang Won Lee Dae Won Jun Tae Hyun Yoon PROTEOMICS – Clinical Applications Immune Landscape Changes in MASLD and the Effects of 11β‐HSD1 Inhibition Revealed by Single‐Cell Mass Cytometry Zayakhuu Gerelkhuu Sehee Park Yun Kim Sang Won Lee Dae Won Jun Tae Hyun Yoon PROTEOMICS – Clinical Applications ABSTRACTBackground: Metabolic dysfunction‐associated steatotic liver disease (MASLD) affects nearly one‐fourth of the global population, yet effective diagnostics and treatments remain limited. Systemic immune dysregulation plays a key role in MASLD pathogenesis, highlighting the value of immune profiling.Methods: In this study, we used high‐dimensional single‐cell mass cytometry (CyTOF) to analyze peripheral blood mononuclear cells (PBMCs) from healthy donors (n = 6), MASLD patients (n = 4), and MASLD patients treated with an 11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1) inhibitor (n = 2). PBMCs were stained with a 29‐marker panel to identify 15 immune cell types and assess cytokine expression.Results: MASLD patients showed increased CD8⁺ T cells, early NK cells, and monocytes, along with reductions in TH2, TH1, late NK, and Treg cells. Cytokine profiling revealed elevated IL‐6 expression in plasmacytoid dendritic cells and late NK cells, indicating systemic inflammation. Automated clustering (PhenoGraph, UMAP) identified NK and phagocytic subsets associated with disease and treatment. Notably, 11β‐HSD1 inhibition led to downregulation of pro‐inflammatory cytokines (e.g., IFN‐γ, IL‐6) and partial restoration of immune subsets.Conclusions: These results offer a high‐resolution view of immune alterations in MASLD and suggest that 11β‐HSD1 inhibition may represent a promising immunomodulatory therapeutic strategy. 10.1002/prca.70022 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| title | Immune Landscape Changes in MASLD and the Effects of 11β‐HSD1 Inhibition Revealed by Single‐Cell Mass Cytometry |
| topic | PROTEOMICS – Clinical Applications |
| url | https://onlinelibrary.wiley.com/doi/10.1002/prca.70022 |