Expansion of effector regulatory T cells in steroid responders of severe alcohol-associated hepatitis

外周血单个核细胞 医学 类固醇 流式细胞术 内科学 免疫学 肝炎 效应器 胃肠病学 内分泌学 体外 生物 激素 生物化学
作者
Min Woo Kang,Soon Kyu Lee,Eun Ji Jang,Jong Geun Park,Deok Hwa Seo,Ji Won Han,Jae-Sung Yoo,Jung Hyun Kwon,Soon Woo Nam,Jeong Won Jang,Jong Young Choi,Seung Kew Yoon,Pil Soo Sung
出处
期刊:Liver Transplantation [Wiley]
卷期号:30 (9): 877-886 被引量:2
标识
DOI:10.1097/lvt.0000000000000378
摘要

While steroid therapy is the preferred treatment for severe alcohol-associated hepatitis, the role of effector regulatory T (eTreg) cells and their association with steroid response and clinical outcomes in these patients remains to be elucidated. We prospectively enrolled 47 consecutive patients with alcohol-associated hepatitis, consisting of severe alcohol-associated hepatitis treated with steroids (n=18; steroid-treated group) and mild alcohol-associated hepatitis (n=29; nontreated group). After isolating peripheral blood mononuclear cells from the patients at enrollment and again 7 days later, the frequency of eTreg cells was examined using flow cytometry. Single-cell RNA sequencing analysis was conducted using paired peripheral blood mononuclear cells. In vitro experiments were also performed to assess phenotype changes and the suppressive function of Treg cells following steroid treatment. The steroid-treated group exhibited significantly higher Model for End-Stage Liver Disease scores than the nontreated group ( p < 0.01). Within the steroid-treated group, the proportion of eTreg cells significantly expanded in the steroid responders (n=13; p = 0.01). Furthermore, a significant positive correlation was observed between the decrease in the Model for End-Stage Liver Disease score and the increase in eTreg cells ( p < 0.05). Single-cell RNA sequencing using paired peripheral blood mononuclear cells (pre-steroid and post-steroid therapy) from a steroid responder revealed gene expression changes in T cells and monocytes, suggesting enhancement of Treg cell function. In vitro results showed an elevation in the proportion of eTreg cells after steroid therapy. In conclusion, our findings suggest that the efficacy of steroid therapy in patients with severe alcohol-associated hepatitis is mediated by an increase in the number of eTreg cells.
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