Molecular immunology · 2025
Characterization of the heterogeneity in oxidative stress and transcriptional programs within the in vivo microenvironment of ulcerative colitis.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Zhuang Yongwei, Ye Ran, Chen Jingyu, Chen Gefei, Chen Luyi, Zhu Yabi, Ye Shufang, Liu Yangyang
Аннотация
OBJECTIVE: Oxidative stress exerts an essential role in the pathogenesis of ulcerative colitis (UC). This study aims to unveil the heterogeneity in oxidative stress among immune cell subpopulations in UC.
METHODS: Human colon epithelial cells were exposed to 100 ng/mL LPS to stimulate UC, which were administrated with antioxidants 500 mM butylated hydroxyanisole or 20 μM N-acetylcysteine. A single-cell atlas was constructed across UC, and heterogeneous cell subpopulations were evaluated at single-cell and bulk levels.
RESULTS: Activation of oxidative stress and inflammatory response, enhanced migration capacity, and impaired tight junction were observed in LPS-induced UC cell models, which were ameliorated by antioxidants. Five cell types: plasma cells, T cells, myeloid cells, and B cells were clustered across UC and control gut biopsies, which were tightly interacted. Myeloid cells were sub-clustered into conventional dendritic cells, M1 macrophages, IL23R+ myeloid cells, mast cells, and follicular dendritic cells; T cells were sub-clustered into Th17, CD4+ naïve T cells, CD8+ cytotoxic T cells, CD4+ exhausted T cells, CD8+ memory T cells, Tregs, and Th1. The heterogeneous myeloid and T cells was confirmed at the single-cell and bulk levels. The activity of oxidative stress was heterogeneous among diverse myeloid cell or T cell subpopulations, with the strongest activity in M1 macrophages and CD4+ exhausted T cells, respectively. It was also found the specific transcriptional programs of M1 macrophages and CD8+ cytotoxic T cells.
CONCLUSION: Overall, our findings unveil the heterogeneity in oxidative stress and transcriptional programs among diverse myeloid and T cell subpopulations in UC.
METHODS: Human colon epithelial cells were exposed to 100 ng/mL LPS to stimulate UC, which were administrated with antioxidants 500 mM butylated hydroxyanisole or 20 μM N-acetylcysteine. A single-cell atlas was constructed across UC, and heterogeneous cell subpopulations were evaluated at single-cell and bulk levels.
RESULTS: Activation of oxidative stress and inflammatory response, enhanced migration capacity, and impaired tight junction were observed in LPS-induced UC cell models, which were ameliorated by antioxidants. Five cell types: plasma cells, T cells, myeloid cells, and B cells were clustered across UC and control gut biopsies, which were tightly interacted. Myeloid cells were sub-clustered into conventional dendritic cells, M1 macrophages, IL23R+ myeloid cells, mast cells, and follicular dendritic cells; T cells were sub-clustered into Th17, CD4+ naïve T cells, CD8+ cytotoxic T cells, CD4+ exhausted T cells, CD8+ memory T cells, Tregs, and Th1. The heterogeneous myeloid and T cells was confirmed at the single-cell and bulk levels. The activity of oxidative stress was heterogeneous among diverse myeloid cell or T cell subpopulations, with the strongest activity in M1 macrophages and CD4+ exhausted T cells, respectively. It was also found the specific transcriptional programs of M1 macrophages and CD8+ cytotoxic T cells.
CONCLUSION: Overall, our findings unveil the heterogeneity in oxidative stress and transcriptional programs among diverse myeloid and T cell subpopulations in UC.