Metabolic heterogeneity caused by HLA-DRB1*04:05 and protective effect of inosine on autoimmune hepatitis
Autoimmune hepatitis (AIH) is an autoimmune disease caused by disruption of liver immune homeostasis. Genetic studies have revealed the predisposition of AIH with the human leukocyte antigen (HLA) region. Recently, metabolomics integrated with genomics has identified many genetic loci of biomedical...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.982186/full |
| _version_ | 1811315682104573952 |
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| author | Fan Yang Leyu Zhou Yi Shen Shenglan Zhao Yanyi Zheng Ruoting Men Xiaoli Fan Li Yang |
| author_facet | Fan Yang Leyu Zhou Yi Shen Shenglan Zhao Yanyi Zheng Ruoting Men Xiaoli Fan Li Yang |
| author_sort | Fan Yang |
| collection | DOAJ |
| description | Autoimmune hepatitis (AIH) is an autoimmune disease caused by disruption of liver immune homeostasis. Genetic studies have revealed the predisposition of AIH with the human leukocyte antigen (HLA) region. Recently, metabolomics integrated with genomics has identified many genetic loci of biomedical interest. However, there is no related report in AIH. In the present study, we found that HLA-DRB1*04:05 was linked to the clinical features and prognosis of AIH in Chinese patients. Furthermore, our patients were divided into DRB1*04:05 positive and DRB1*04:05 negative groups and the metabolic profiling was done by HPLC/MS. We chose inosine, one of the highly altered metabolites, to explore the effect on an acute severe hepatitis murine model. The results showed that inosine treatment attenuated hepatocyte apoptosis, enhanced antioxidant ability and inhibited the activation and glycolysis of CD4+ T cell. We propose that inosine participates in the regulation of AIH through its protective effect on hepatocytes and inhibition of overactivated immune cells, which might provide a potential novel approach in treating acute form of AIH. |
| first_indexed | 2024-04-13T11:35:18Z |
| format | Article |
| id | doaj.art-914ff2980b244b5db71b409572634f92 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T11:35:18Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-914ff2980b244b5db71b409572634f922022-12-22T02:48:28ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-08-011310.3389/fimmu.2022.982186982186Metabolic heterogeneity caused by HLA-DRB1*04:05 and protective effect of inosine on autoimmune hepatitisFan YangLeyu ZhouYi ShenShenglan ZhaoYanyi ZhengRuoting MenXiaoli FanLi YangAutoimmune hepatitis (AIH) is an autoimmune disease caused by disruption of liver immune homeostasis. Genetic studies have revealed the predisposition of AIH with the human leukocyte antigen (HLA) region. Recently, metabolomics integrated with genomics has identified many genetic loci of biomedical interest. However, there is no related report in AIH. In the present study, we found that HLA-DRB1*04:05 was linked to the clinical features and prognosis of AIH in Chinese patients. Furthermore, our patients were divided into DRB1*04:05 positive and DRB1*04:05 negative groups and the metabolic profiling was done by HPLC/MS. We chose inosine, one of the highly altered metabolites, to explore the effect on an acute severe hepatitis murine model. The results showed that inosine treatment attenuated hepatocyte apoptosis, enhanced antioxidant ability and inhibited the activation and glycolysis of CD4+ T cell. We propose that inosine participates in the regulation of AIH through its protective effect on hepatocytes and inhibition of overactivated immune cells, which might provide a potential novel approach in treating acute form of AIH.https://www.frontiersin.org/articles/10.3389/fimmu.2022.982186/fullautoimmune hepatitisHLA-DRB1*04:05metabolomicsinosineCD4+ T cell |
| spellingShingle | Fan Yang Leyu Zhou Yi Shen Shenglan Zhao Yanyi Zheng Ruoting Men Xiaoli Fan Li Yang Metabolic heterogeneity caused by HLA-DRB1*04:05 and protective effect of inosine on autoimmune hepatitis Frontiers in Immunology autoimmune hepatitis HLA-DRB1*04:05 metabolomics inosine CD4+ T cell |
| title | Metabolic heterogeneity caused by HLA-DRB1*04:05 and protective effect of inosine on autoimmune hepatitis |
| title_full | Metabolic heterogeneity caused by HLA-DRB1*04:05 and protective effect of inosine on autoimmune hepatitis |
| title_fullStr | Metabolic heterogeneity caused by HLA-DRB1*04:05 and protective effect of inosine on autoimmune hepatitis |
| title_full_unstemmed | Metabolic heterogeneity caused by HLA-DRB1*04:05 and protective effect of inosine on autoimmune hepatitis |
| title_short | Metabolic heterogeneity caused by HLA-DRB1*04:05 and protective effect of inosine on autoimmune hepatitis |
| title_sort | metabolic heterogeneity caused by hla drb1 04 05 and protective effect of inosine on autoimmune hepatitis |
| topic | autoimmune hepatitis HLA-DRB1*04:05 metabolomics inosine CD4+ T cell |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.982186/full |
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