Frontiers in Immunology (Jun 2024)
Impaired arginine/ornithine metabolism drives severe HFMD by promoting cytokine storm
- Yaozhong Zhang,
- Yaozhong Zhang,
- Yaozhong Zhang,
- Qingqing Yang,
- Qi Peng,
- Qi Peng,
- Qi Peng,
- Zhihua Tian,
- Fen Lv,
- Fen Lv,
- Fen Lv,
- Xiaomei Zeng,
- Xiaomei Zeng,
- Xiaomei Zeng,
- Zaixue Jiang,
- Zaixue Jiang,
- Zaixue Jiang,
- Qingqiu Cheng,
- Qingqiu Cheng,
- Qingqiu Cheng,
- Lijun Yang,
- Baimao Zhong,
- Baimao Zhong,
- Baimao Zhong,
- Xiaomei Lu,
- Xiaomei Lu,
- Xiaomei Lu,
- Yinghua Zhu,
- Yinghua Zhu,
- Yinghua Zhu
Affiliations
- Yaozhong Zhang
- Department of Genetic Medicine, Dongguan Children’s Hospital Affiliated to Guangdong Medical University, Dongguan, China
- Yaozhong Zhang
- Department of Medical and Molecular Genetics, Dongguan Institute of Pediatrics, Dongguan, China
- Yaozhong Zhang
- Department of Genetics, Key Laboratory for Children’s Genetics and Infectious Diseases of Dongguan, Dongguan, China
- Qingqing Yang
- Department of Genetic Medicine, Dongguan Children’s Hospital Affiliated to Guangdong Medical University, Dongguan, China
- Qi Peng
- Department of Genetic Medicine, Dongguan Children’s Hospital Affiliated to Guangdong Medical University, Dongguan, China
- Qi Peng
- Department of Medical and Molecular Genetics, Dongguan Institute of Pediatrics, Dongguan, China
- Qi Peng
- Department of Genetics, Key Laboratory for Children’s Genetics and Infectious Diseases of Dongguan, Dongguan, China
- Zhihua Tian
- Department of Genetic Medicine, Dongguan Children’s Hospital Affiliated to Guangdong Medical University, Dongguan, China
- Fen Lv
- Department of Genetic Medicine, Dongguan Children’s Hospital Affiliated to Guangdong Medical University, Dongguan, China
- Fen Lv
- Department of Medical and Molecular Genetics, Dongguan Institute of Pediatrics, Dongguan, China
- Fen Lv
- Department of Genetics, Key Laboratory for Children’s Genetics and Infectious Diseases of Dongguan, Dongguan, China
- Xiaomei Zeng
- Department of Genetic Medicine, Dongguan Children’s Hospital Affiliated to Guangdong Medical University, Dongguan, China
- Xiaomei Zeng
- Department of Medical and Molecular Genetics, Dongguan Institute of Pediatrics, Dongguan, China
- Xiaomei Zeng
- Department of Genetics, Key Laboratory for Children’s Genetics and Infectious Diseases of Dongguan, Dongguan, China
- Zaixue Jiang
- Department of Genetic Medicine, Dongguan Children’s Hospital Affiliated to Guangdong Medical University, Dongguan, China
- Zaixue Jiang
- Department of Medical and Molecular Genetics, Dongguan Institute of Pediatrics, Dongguan, China
- Zaixue Jiang
- Department of Genetics, Key Laboratory for Children’s Genetics and Infectious Diseases of Dongguan, Dongguan, China
- Qingqiu Cheng
- Department of Genetic Medicine, Dongguan Children’s Hospital Affiliated to Guangdong Medical University, Dongguan, China
- Qingqiu Cheng
- Department of Medical and Molecular Genetics, Dongguan Institute of Pediatrics, Dongguan, China
- Qingqiu Cheng
- Department of Genetics, Key Laboratory for Children’s Genetics and Infectious Diseases of Dongguan, Dongguan, China
- Lijun Yang
- Department of Genetic Medicine, Dongguan Children’s Hospital Affiliated to Guangdong Medical University, Dongguan, China
- Baimao Zhong
- Department of Genetic Medicine, Dongguan Children’s Hospital Affiliated to Guangdong Medical University, Dongguan, China
- Baimao Zhong
- Department of Medical and Molecular Genetics, Dongguan Institute of Pediatrics, Dongguan, China
- Baimao Zhong
- Department of Genetics, Key Laboratory for Children’s Genetics and Infectious Diseases of Dongguan, Dongguan, China
- Xiaomei Lu
- Department of Genetic Medicine, Dongguan Children’s Hospital Affiliated to Guangdong Medical University, Dongguan, China
- Xiaomei Lu
- Department of Medical and Molecular Genetics, Dongguan Institute of Pediatrics, Dongguan, China
- Xiaomei Lu
- Department of Genetics, Key Laboratory for Children’s Genetics and Infectious Diseases of Dongguan, Dongguan, China
- Yinghua Zhu
- Department of Genetic Medicine, Dongguan Children’s Hospital Affiliated to Guangdong Medical University, Dongguan, China
- Yinghua Zhu
- Department of Medical and Molecular Genetics, Dongguan Institute of Pediatrics, Dongguan, China
- Yinghua Zhu
- Department of Genetics, Key Laboratory for Children’s Genetics and Infectious Diseases of Dongguan, Dongguan, China
- DOI
- https://doi.org/10.3389/fimmu.2024.1407035
- Journal volume & issue
-
Vol. 15
Abstract
IntroductionThe Hand, Foot and Mouth Disease (HFMD), caused by enterovirus 71 infection, is a global public health emergency. Severe HFMD poses a significant threat to the life and well-being of children. Numerous studies have indicated that the occurrence of severe HFMD is associated with cytokine storm. However, the precise molecular mechanism underlying cytokine storm development remains elusive, and there are currently no safe and effective treatments available for severe HFMD in children.MethodsIn this study, we established a mouse model of severe HFMD to investigate the molecular mechanisms driving cytokine storm. We specifically analyzed metabolic disturbances, focusing on arginine/ornithine metabolism, and assessed the potential therapeutic effects of spermine, an ornithine metabolite.ResultsOur results identified disturbances in arginine/ornithine metabolism as a pivotal factor driving cytokine storm onset in severe HFMD cases. Additionally, we discovered that spermine effectively mitigated the inflammatory injury phenotype observed in mice with severe HFMD.DiscussionIn conclusion, our findings provide novel insights into the molecular mechanisms underlying severe HFMD from a metabolic perspective while offering a promising new strategy for its safe and effective treatment.
Keywords
