Impaired mitochondria of Tregs decreases OXPHOS-derived ATP in primary immune thrombocytopenia with positive plasma pathogens detected by metagenomic sequencing
Abstract Background Primary immune thrombocytopenia (ITP) is an autoimmune disease. Some ITP patients are associated with pathogen infection undetected with conventional technologies. Investigating the changes of T cells and potential metabolic mechanism are important for better understanding of ITP...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-09-01
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| Series: | Experimental Hematology & Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40164-022-00304-y |
| _version_ | 1817994029608992768 |
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| author | Yanxia Zhan Jingjing Cao Lili Ji Miaomiao Zhang Qi Shen Pengcheng Xu Xibing Zhuang Shanshan Qin Fanli Hua Lihua Sun Feng Li Hao Chen Yunfeng Cheng |
| author_facet | Yanxia Zhan Jingjing Cao Lili Ji Miaomiao Zhang Qi Shen Pengcheng Xu Xibing Zhuang Shanshan Qin Fanli Hua Lihua Sun Feng Li Hao Chen Yunfeng Cheng |
| author_sort | Yanxia Zhan |
| collection | DOAJ |
| description | Abstract Background Primary immune thrombocytopenia (ITP) is an autoimmune disease. Some ITP patients are associated with pathogen infection undetected with conventional technologies. Investigating the changes of T cells and potential metabolic mechanism are important for better understanding of ITP. Methods The study enrolled 75 newly diagnosed ITP patients. The pathogens of patients were detected by metagenomic next-generation sequencing (mNGS). Plasma lipids were measured by liquid chromatography-mass spectrometry (LC–MS). CD4 T cell and CD8 T cell were analyzed using flow cytometry. Mitochondrial reactive oxygen species (ROS) and mitochondrial membrane potential were measured by flow cytometry. Seahorse XF real-time ATP rate assay was used to investigate the change of cellular metabolism. Results Positive plasma pathogens were detected in seven ITP patients. Of them, 5 (71.4%) positive pathogen-ITP patients were no response (NR) after first-line treatment with corticosteroids. Regulatory T cells (Tregs) increased significantly in positive pathogen-ITP patients compared to negative pathogen-ITP patients and healthy controls (HC). Mitochondrial membrane potential of Th17 and Tregs were decreased in positive pathogen-ITP and negative pathogen-ITP patients, compared to HC (all p < 0.05). The overall metabolism flux of positive pathogen-ITP patients was decreased, as compared to HC (p = 0.004), of them a higher proportion of glycolysis-derived ATP and a smaller proportion of oxidative phosphorylation (OXPHOS)-derived ATP were found in Tregs. The ATP rate index of Tregs was decreased significantly in positive pathogen-ITP patients compared to negative pathogen-ITP patients and HC (p < 0.05). Conclusions Impaired mitochondria function of Tregs in positive pathogen-ITP patients caused a decrease of OXPHOS-derived ATP and overall metabolism flux that might be the cause of steroid resistance in ITP patients. |
| first_indexed | 2024-04-14T01:47:31Z |
| format | Article |
| id | doaj.art-0ea3f853745046d49c6e173a854a9141 |
| institution | Directory Open Access Journal |
| issn | 2162-3619 |
| language | English |
| last_indexed | 2024-04-14T01:47:31Z |
| publishDate | 2022-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Experimental Hematology & Oncology |
| spelling | doaj.art-0ea3f853745046d49c6e173a854a91412022-12-22T02:19:28ZengBMCExperimental Hematology & Oncology2162-36192022-09-0111111410.1186/s40164-022-00304-yImpaired mitochondria of Tregs decreases OXPHOS-derived ATP in primary immune thrombocytopenia with positive plasma pathogens detected by metagenomic sequencingYanxia Zhan0Jingjing Cao1Lili Ji2Miaomiao Zhang3Qi Shen4Pengcheng Xu5Xibing Zhuang6Shanshan Qin7Fanli Hua8Lihua Sun9Feng Li10Hao Chen11Yunfeng Cheng12Department of Hematology, Zhongshan Hospital, Fudan UniversityDepartment of Hematology, Zhongshan Hospital, Fudan UniversityDepartment of Hematology, Zhongshan Hospital, Fudan UniversityInstitute of Clinical Science, Zhongshan Hospital, Fudan UniversityInstitute of Clinical Science, Zhongshan Hospital, Fudan UniversityDepartment of Hematology, Zhongshan Hospital, Fudan UniversityDepartment of Hematology, Zhongshan Hospital, Fudan UniversityDepartment of Hematology, Zhongshan Hospital, Fudan UniversityDepartment of Hematology, Zhongshan Hospital Qingpu Branch, Fudan UniversityDepartment of Hematology, Zhongshan Hospital Qingpu Branch, Fudan UniversityDepartment of Hematology, Zhongshan Hospital, Fudan UniversityDepartment of Thoracic Surgery, Zhongshan Hospital Xuhui Branch, Fudan UniversityDepartment of Hematology, Zhongshan Hospital, Fudan UniversityAbstract Background Primary immune thrombocytopenia (ITP) is an autoimmune disease. Some ITP patients are associated with pathogen infection undetected with conventional technologies. Investigating the changes of T cells and potential metabolic mechanism are important for better understanding of ITP. Methods The study enrolled 75 newly diagnosed ITP patients. The pathogens of patients were detected by metagenomic next-generation sequencing (mNGS). Plasma lipids were measured by liquid chromatography-mass spectrometry (LC–MS). CD4 T cell and CD8 T cell were analyzed using flow cytometry. Mitochondrial reactive oxygen species (ROS) and mitochondrial membrane potential were measured by flow cytometry. Seahorse XF real-time ATP rate assay was used to investigate the change of cellular metabolism. Results Positive plasma pathogens were detected in seven ITP patients. Of them, 5 (71.4%) positive pathogen-ITP patients were no response (NR) after first-line treatment with corticosteroids. Regulatory T cells (Tregs) increased significantly in positive pathogen-ITP patients compared to negative pathogen-ITP patients and healthy controls (HC). Mitochondrial membrane potential of Th17 and Tregs were decreased in positive pathogen-ITP and negative pathogen-ITP patients, compared to HC (all p < 0.05). The overall metabolism flux of positive pathogen-ITP patients was decreased, as compared to HC (p = 0.004), of them a higher proportion of glycolysis-derived ATP and a smaller proportion of oxidative phosphorylation (OXPHOS)-derived ATP were found in Tregs. The ATP rate index of Tregs was decreased significantly in positive pathogen-ITP patients compared to negative pathogen-ITP patients and HC (p < 0.05). Conclusions Impaired mitochondria function of Tregs in positive pathogen-ITP patients caused a decrease of OXPHOS-derived ATP and overall metabolism flux that might be the cause of steroid resistance in ITP patients.https://doi.org/10.1186/s40164-022-00304-yImmune thrombocytopeniaTregs (Regulatory T cells)GlycolysisOxidative phosphorylationPathogens |
| spellingShingle | Yanxia Zhan Jingjing Cao Lili Ji Miaomiao Zhang Qi Shen Pengcheng Xu Xibing Zhuang Shanshan Qin Fanli Hua Lihua Sun Feng Li Hao Chen Yunfeng Cheng Impaired mitochondria of Tregs decreases OXPHOS-derived ATP in primary immune thrombocytopenia with positive plasma pathogens detected by metagenomic sequencing Experimental Hematology & Oncology Immune thrombocytopenia Tregs (Regulatory T cells) Glycolysis Oxidative phosphorylation Pathogens |
| title | Impaired mitochondria of Tregs decreases OXPHOS-derived ATP in primary immune thrombocytopenia with positive plasma pathogens detected by metagenomic sequencing |
| title_full | Impaired mitochondria of Tregs decreases OXPHOS-derived ATP in primary immune thrombocytopenia with positive plasma pathogens detected by metagenomic sequencing |
| title_fullStr | Impaired mitochondria of Tregs decreases OXPHOS-derived ATP in primary immune thrombocytopenia with positive plasma pathogens detected by metagenomic sequencing |
| title_full_unstemmed | Impaired mitochondria of Tregs decreases OXPHOS-derived ATP in primary immune thrombocytopenia with positive plasma pathogens detected by metagenomic sequencing |
| title_short | Impaired mitochondria of Tregs decreases OXPHOS-derived ATP in primary immune thrombocytopenia with positive plasma pathogens detected by metagenomic sequencing |
| title_sort | impaired mitochondria of tregs decreases oxphos derived atp in primary immune thrombocytopenia with positive plasma pathogens detected by metagenomic sequencing |
| topic | Immune thrombocytopenia Tregs (Regulatory T cells) Glycolysis Oxidative phosphorylation Pathogens |
| url | https://doi.org/10.1186/s40164-022-00304-y |
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