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乳杆菌通过肠道微生物群介导的滤泡辅助 T 细胞改善泼尼松对自身免疫性肝炎的作用。

Lactobacillus improves the effects of prednisone on autoimmune hepatitis via gut microbiota-mediated follicular helper T cells.

机构信息

Department of Digestive Diseases, The First People's Hospital of Changzhou, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, Jiangsu, China.

Department of Pediatrics, The Second People's Hospital of Changzhou, Affiliated Hospital of Nanjing Medical University, Changzhou, 213003, Jiangsu, China.

出版信息

Cell Commun Signal. 2022 Jun 3;20(1):83. doi: 10.1186/s12964-021-00819-7.

DOI:10.1186/s12964-021-00819-7
PMID:35658901
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9166466/
Abstract

BACKGROUND

Autoimmune hepatitis (AIH) is a chronic, immune-mediated liver dysfunction. The gut microbiota and T follicular helper (Tfh) cells play critical roles in the immunopathogenesis and progression of AIH. We aimed to investigate the effect of gut microbiota combined with prednisone therapy on Tfh cell response in AIH.

METHODS

Samples from AIH patients and mouse model of experimental autoimmune hepatitis (EAH) were analyzed using real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, western blotting, flow cytometry, and hematoxylin-eosin staining to determine the role of gut microbiota on AIH.

RESULTS

Lactobacillus significantly increased the levels of Bacteroides fragilis, Clostridium, Clostridium leptum, Bifidobacterium, and Lactobacillus and significantly enhanced the suppressive effects of prednisone on the levels of AIH clinical indexes in AIH patients. Lactobacillus exerts the same prptective effects as prednisone in EAH mice and enhanced the effects of prednisone. Lactobacillus also reinforced the inhibitory effects of prednisone on the levels of serum IL-21 and the proportions of Tfh cells in peripheral blood mononuclear cells. Mechanistically, prednisone and Lactobacillus regulated Tfh cell response in EAH mice in an MyD88/NF-κB pathway-dependent manner.

CONCLUSION

Our results suggested a therapeutic potential of Lactobacillus in the prednisone-combined treatment of AIH. Video Abstract.

摘要

背景

自身免疫性肝炎（AIH）是一种慢性、免疫介导的肝功能障碍。肠道微生物群和滤泡辅助性 T 细胞（Tfh）在 AIH 的免疫发病机制和进展中起着关键作用。我们旨在研究肠道微生物群联合泼尼松治疗对 AIH 中 Tfh 细胞反应的影响。

方法

使用实时定量聚合酶链反应、酶联免疫吸附试验、western blot、流式细胞术和苏木精-伊红染色分析 AIH 患者和实验性自身免疫性肝炎（EAH）小鼠模型的样本，以确定肠道微生物群对 AIH 的作用。

结果

乳杆菌显著增加脆弱拟杆菌、梭菌、梭状芽孢杆菌、双歧杆菌和乳酸杆菌的水平，并显著增强泼尼松对 AIH 患者 AIH 临床指标水平的抑制作用。乳杆菌在 EAH 小鼠中发挥与泼尼松相同的保护作用，并增强了泼尼松的作用。乳杆菌还增强了泼尼松对血清 IL-21 水平和外周血单个核细胞中 Tfh 细胞比例的抑制作用。在机制上，泼尼松和乳杆菌通过 MyD88/NF-κB 途径调节 EAH 小鼠中的 Tfh 细胞反应。

结论

我们的结果表明，乳杆菌在泼尼松联合治疗 AIH 方面具有治疗潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5092/9166466/522cd6280e73/12964_2021_819_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5092/9166466/89587106d228/12964_2021_819_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5092/9166466/3ee53a6b46a2/12964_2021_819_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5092/9166466/61b2c03ada03/12964_2021_819_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5092/9166466/f31871b97472/12964_2021_819_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5092/9166466/743cfce5e2ce/12964_2021_819_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5092/9166466/3c784c39b042/12964_2021_819_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5092/9166466/522cd6280e73/12964_2021_819_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5092/9166466/89587106d228/12964_2021_819_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5092/9166466/3ee53a6b46a2/12964_2021_819_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5092/9166466/61b2c03ada03/12964_2021_819_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5092/9166466/f31871b97472/12964_2021_819_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5092/9166466/743cfce5e2ce/12964_2021_819_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5092/9166466/3c784c39b042/12964_2021_819_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5092/9166466/522cd6280e73/12964_2021_819_Fig7_HTML.jpg

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