PMID- 35990653
OWN - NLM
STAT- MEDLINE
DCOM- 20220823
LR  - 20220912
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 13
DP  - 2022
TI  - Metabolic heterogeneity caused by HLA-DRB1*04:05 and protective effect of inosine 
      on autoimmune hepatitis.
PG  - 982186
LID - 10.3389/fimmu.2022.982186 [doi]
LID - 982186
AB  - 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.
CI  - Copyright (c) 2022 Yang, Zhou, Shen, Zhao, Zheng, Men, Fan and Yang.
FAU - Yang, Fan
AU  - Yang F
AD  - Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal 
      Cancer, Department of Gastroenterology and Hepatology, West China Hospital, 
      Sichuan University, Chengdu, China.
FAU - Zhou, Leyu
AU  - Zhou L
AD  - Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal 
      Cancer, Department of Gastroenterology and Hepatology, West China Hospital, 
      Sichuan University, Chengdu, China.
FAU - Shen, Yi
AU  - Shen Y
AD  - Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal 
      Cancer, Department of Gastroenterology and Hepatology, West China Hospital, 
      Sichuan University, Chengdu, China.
FAU - Zhao, Shenglan
AU  - Zhao S
AD  - Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal 
      Cancer, Department of Gastroenterology and Hepatology, West China Hospital, 
      Sichuan University, Chengdu, China.
FAU - Zheng, Yanyi
AU  - Zheng Y
AD  - Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal 
      Cancer, Department of Gastroenterology and Hepatology, West China Hospital, 
      Sichuan University, Chengdu, China.
FAU - Men, Ruoting
AU  - Men R
AD  - Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal 
      Cancer, Department of Gastroenterology and Hepatology, West China Hospital, 
      Sichuan University, Chengdu, China.
FAU - Fan, Xiaoli
AU  - Fan X
AD  - Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal 
      Cancer, Department of Gastroenterology and Hepatology, West China Hospital, 
      Sichuan University, Chengdu, China.
FAU - Yang, Li
AU  - Yang L
AD  - Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal 
      Cancer, Department of Gastroenterology and Hepatology, West China Hospital, 
      Sichuan University, Chengdu, China.
LA  - eng
PT  - Journal Article
DEP - 20220805
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (HLA-DRB1*04 antigen)
RN  - 0 (Protective Agents)
RN  - 5A614L51CT (Inosine)
SB  - IM
MH  - Alleles
MH  - Animals
MH  - Genetic Predisposition to Disease
MH  - *HLA-DRB1 Chains/genetics/metabolism
MH  - *Hepatitis, Autoimmune/genetics/metabolism
MH  - Hepatocytes/drug effects/metabolism
MH  - Humans
MH  - *Inosine/therapeutic use
MH  - Metabolome
MH  - Mice
MH  - Prognosis
MH  - *Protective Agents/therapeutic use
PMC - PMC9389112
OTO - NOTNLM
OT  - CD4+ T cell
OT  - HLA-DRB1*04:05
OT  - autoimmune hepatitis
OT  - inosine
OT  - metabolomics
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/08/23 06:00
MHDA- 2022/08/24 06:00
PMCR- 2022/01/01
CRDT- 2022/08/22 03:58
PHST- 2022/06/30 00:00 [received]
PHST- 2022/07/15 00:00 [accepted]
PHST- 2022/08/22 03:58 [entrez]
PHST- 2022/08/23 06:00 [pubmed]
PHST- 2022/08/24 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2022.982186 [doi]
PST - epublish
SO  - Front Immunol. 2022 Aug 5;13:982186. doi: 10.3389/fimmu.2022.982186. eCollection 
      2022.