NK cell-derived exosomes carry miR-207 and alleviate depression-like symptoms in mice
Abstract Background Depression is a common mental disease that mainly manifests as bad mood, decreased interest, pessimism, slow thinking, lack of initiative, poor diet and sleep. Patients with severe depression have suicidal tendencies. Exosomes are small vesicles released by the fusion of a multiv...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-04-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12974-020-01787-4 |
| _version_ | 1819011253720317952 |
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| author | Dongping Li Ying Wang Xinrong Jin Die Hu Chunlei Xia Hanmei Xu Jialiang Hu |
| author_facet | Dongping Li Ying Wang Xinrong Jin Die Hu Chunlei Xia Hanmei Xu Jialiang Hu |
| author_sort | Dongping Li |
| collection | DOAJ |
| description | Abstract Background Depression is a common mental disease that mainly manifests as bad mood, decreased interest, pessimism, slow thinking, lack of initiative, poor diet and sleep. Patients with severe depression have suicidal tendencies. Exosomes are small vesicles released by the fusion of a multivesicular body and membranes, and they contain specific proteins, nucleic acids, and lipids related to the cells from which they originate. MicroRNAs (miRNAs) are 20–24 nt RNAs that can be packaged into exosomes and can play important regulatory roles. Astrocytes are the most abundant cell population in the central nervous system and have a close link to depression. Astrocyte activation could result in the release of inflammatory cytokines, including IL-1β, IL-6, and TNF-α, which could promote the symptoms of depression. In previous research, our team confirmed that NK cells regulate depression in mice. Here, we propose that miRNA in the exosomes from NK cells performs this antidepressant function. Methods Exosomes from NK cells were shown by in vivo and in vitro experiments to alleviate symptoms of chronic mild stress in mice and decrease pro-inflammatory cytokines release from astrocytes. The production of pro-inflammatory cytokines was assessed by ELISA. Microarray analysis was used to identify critical miRNAs. Luciferase reporter assays, qPCR, and other experiments were used to prove that exosomal miR-207 has an important role in alleviating the symptoms of stress in mice. Results MiRNA-containing exosomes from NK cells could alleviate symptoms of chronic mild stress in mice. In vivo experiments showed that these exosomes decreased the levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) released by astrocytes. By microarray analysis of exosome miRNA profiles, miR-207 was found to be overexpressed in exosomes derived from unstressed mice. Experiments confirmed that miR-207 directly targets TLR4 interactor with leucine-rich repeats (Tril) and inhibits NF-κB signaling in astrocytes. MiR-207 could decrease the release of pro-inflammatory cytokines and inhibit expression of Tril in vitro. In vivo experiments revealed that exosomes with low miR-207 levels showed decreased antidepressant activity. Conclusion Collectively, our findings revealed that exosomal miR-207 alleviated symptoms of depression in stressed mice by targeting Tril to inhibit NF-κB signaling in astrocytes. |
| first_indexed | 2024-12-21T01:25:13Z |
| format | Article |
| id | doaj.art-747a16528ce347c79a32d1cd5d731190 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-12-21T01:25:13Z |
| publishDate | 2020-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-747a16528ce347c79a32d1cd5d7311902022-12-21T19:20:31ZengBMCJournal of Neuroinflammation1742-20942020-04-0117111910.1186/s12974-020-01787-4NK cell-derived exosomes carry miR-207 and alleviate depression-like symptoms in miceDongping Li0Ying Wang1Xinrong Jin2Die Hu3Chunlei Xia4Hanmei Xu5Jialiang Hu6The Engineering Research Center of Synthetic Polypeptide Discovery and Evaluation of Jiangsu ProvinceThe Engineering Research Center of Synthetic Polypeptide Discovery and Evaluation of Jiangsu ProvinceThe Engineering Research Center of Synthetic Polypeptide Discovery and Evaluation of Jiangsu ProvinceThe Engineering Research Center of Synthetic Polypeptide Discovery and Evaluation of Jiangsu ProvinceThe Engineering Research Center of Synthetic Polypeptide Discovery and Evaluation of Jiangsu ProvinceThe Engineering Research Center of Synthetic Polypeptide Discovery and Evaluation of Jiangsu ProvinceThe Engineering Research Center of Synthetic Polypeptide Discovery and Evaluation of Jiangsu ProvinceAbstract Background Depression is a common mental disease that mainly manifests as bad mood, decreased interest, pessimism, slow thinking, lack of initiative, poor diet and sleep. Patients with severe depression have suicidal tendencies. Exosomes are small vesicles released by the fusion of a multivesicular body and membranes, and they contain specific proteins, nucleic acids, and lipids related to the cells from which they originate. MicroRNAs (miRNAs) are 20–24 nt RNAs that can be packaged into exosomes and can play important regulatory roles. Astrocytes are the most abundant cell population in the central nervous system and have a close link to depression. Astrocyte activation could result in the release of inflammatory cytokines, including IL-1β, IL-6, and TNF-α, which could promote the symptoms of depression. In previous research, our team confirmed that NK cells regulate depression in mice. Here, we propose that miRNA in the exosomes from NK cells performs this antidepressant function. Methods Exosomes from NK cells were shown by in vivo and in vitro experiments to alleviate symptoms of chronic mild stress in mice and decrease pro-inflammatory cytokines release from astrocytes. The production of pro-inflammatory cytokines was assessed by ELISA. Microarray analysis was used to identify critical miRNAs. Luciferase reporter assays, qPCR, and other experiments were used to prove that exosomal miR-207 has an important role in alleviating the symptoms of stress in mice. Results MiRNA-containing exosomes from NK cells could alleviate symptoms of chronic mild stress in mice. In vivo experiments showed that these exosomes decreased the levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) released by astrocytes. By microarray analysis of exosome miRNA profiles, miR-207 was found to be overexpressed in exosomes derived from unstressed mice. Experiments confirmed that miR-207 directly targets TLR4 interactor with leucine-rich repeats (Tril) and inhibits NF-κB signaling in astrocytes. MiR-207 could decrease the release of pro-inflammatory cytokines and inhibit expression of Tril in vitro. In vivo experiments revealed that exosomes with low miR-207 levels showed decreased antidepressant activity. Conclusion Collectively, our findings revealed that exosomal miR-207 alleviated symptoms of depression in stressed mice by targeting Tril to inhibit NF-κB signaling in astrocytes.http://link.springer.com/article/10.1186/s12974-020-01787-4Exosomal miR-207TrilNK cellsDepressionInflammatory |
| spellingShingle | Dongping Li Ying Wang Xinrong Jin Die Hu Chunlei Xia Hanmei Xu Jialiang Hu NK cell-derived exosomes carry miR-207 and alleviate depression-like symptoms in mice Journal of Neuroinflammation Exosomal miR-207 Tril NK cells Depression Inflammatory |
| title | NK cell-derived exosomes carry miR-207 and alleviate depression-like symptoms in mice |
| title_full | NK cell-derived exosomes carry miR-207 and alleviate depression-like symptoms in mice |
| title_fullStr | NK cell-derived exosomes carry miR-207 and alleviate depression-like symptoms in mice |
| title_full_unstemmed | NK cell-derived exosomes carry miR-207 and alleviate depression-like symptoms in mice |
| title_short | NK cell-derived exosomes carry miR-207 and alleviate depression-like symptoms in mice |
| title_sort | nk cell derived exosomes carry mir 207 and alleviate depression like symptoms in mice |
| topic | Exosomal miR-207 Tril NK cells Depression Inflammatory |
| url | http://link.springer.com/article/10.1186/s12974-020-01787-4 |
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