Interleukin‐23 Secreted by Activated Macrophages Drives γδT Cell Production of Interleukin‐17 to Aggravate Secondary Injury After Intracerebral Hemorrhage
BackgroundNeuroinflammation plays a key role in intracerebral hemorrhage (ICH)–induced secondary brain injury, but the specific roles of peripheral inflammatory cells such as macrophages and lymphocytes remain unknown. The purpose of this study was to explore the roles of macrophages, T lymphocytes,...
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Wiley
2016-10-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.116.004340 |
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| author | Qi Zhong Kai Zhou Qiao‐Li Liang Sen Lin Yan‐Chun Wang Xiao‐Yi Xiong Zhao‐You Meng Ting Zhao Wen‐Yao Zhu Yuan‐Rui Yang Mao‐Fan Liao Qiu‐Wen Gong Liang Liu Ao Xiong Junwei Hao Jian Wang Qing‐Wu Yang |
| author_facet | Qi Zhong Kai Zhou Qiao‐Li Liang Sen Lin Yan‐Chun Wang Xiao‐Yi Xiong Zhao‐You Meng Ting Zhao Wen‐Yao Zhu Yuan‐Rui Yang Mao‐Fan Liao Qiu‐Wen Gong Liang Liu Ao Xiong Junwei Hao Jian Wang Qing‐Wu Yang |
| author_sort | Qi Zhong |
| collection | DOAJ |
| description | BackgroundNeuroinflammation plays a key role in intracerebral hemorrhage (ICH)–induced secondary brain injury, but the specific roles of peripheral inflammatory cells such as macrophages and lymphocytes remain unknown. The purpose of this study was to explore the roles of macrophages, T lymphocytes, and the cytokines they secrete as potential targets for treating secondary brain injury after ICH. Methods and ResultsOur results showed that peripheral macrophages and T lymphocytes successively infiltrated the brain, with macrophage counts peaking 1 day after ICH and T‐lymphocyte counts peaking after 4 days. These peaks in cellular infiltration corresponded to increases in interleukin (IL)‐23 and IL‐17 expression, respectively. We found that hemoglobin from the hematoma activated IL‐23 secretion by infiltrating macrophages by inducing the formation of toll‐like receptor (TLR) 2/4 heterodimer. This increased IL‐23 expression stimulated γδT‐cell production of IL‐17, which increased brain edema and neurologic deficits in the model mice as a proinflammatory factor. Finally, we found that sparstolonin B (SsnB) could ameliorate brain edema and neurologic deficits in ICH model mice via inhibition of TLR2/TLR4 heterodimer formation, and notably, SsnB interacted with myeloid differentiation factor 88 Arg196. ConclusionsTogether, our results reveal the importance of the IL‐23/IL‐17 inflammatory axis in secondary brain injury after ICH and thus provide a new therapeutic target for ICH treatment. |
| first_indexed | 2024-12-18T10:49:00Z |
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| id | doaj.art-d2bacaa3ff504407b6bf925cfb45ef11 |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-12-18T10:49:00Z |
| publishDate | 2016-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-d2bacaa3ff504407b6bf925cfb45ef112022-12-21T21:10:30ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802016-10-0151010.1161/JAHA.116.004340Interleukin‐23 Secreted by Activated Macrophages Drives γδT Cell Production of Interleukin‐17 to Aggravate Secondary Injury After Intracerebral HemorrhageQi Zhong0Kai Zhou1Qiao‐Li Liang2Sen Lin3Yan‐Chun Wang4Xiao‐Yi Xiong5Zhao‐You Meng6Ting Zhao7Wen‐Yao Zhu8Yuan‐Rui Yang9Mao‐Fan Liao10Qiu‐Wen Gong11Liang Liu12Ao Xiong13Junwei Hao14Jian Wang15Qing‐Wu Yang16Department of Neurology, Xinqiao Hospital, the Third Military Medical University, Chongqing, ChinaDepartment of Neurology, Xinqiao Hospital, the Third Military Medical University, Chongqing, ChinaNanjing University of Chinese Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing, ChinaDepartment of Anatomy, Histology and Embryology, Chengdu Medical College, Chengdu, ChinaDepartment of Neurology, Xinqiao Hospital, the Third Military Medical University, Chongqing, ChinaDepartment of Neurology, Xinqiao Hospital, the Third Military Medical University, Chongqing, ChinaDepartment of Neurology, Xinqiao Hospital, the Third Military Medical University, Chongqing, ChinaDepartment of Neurology, Xinqiao Hospital, the Third Military Medical University, Chongqing, ChinaDepartment of Neurology, Xinqiao Hospital, the Third Military Medical University, Chongqing, ChinaDepartment of Neurology, Xinqiao Hospital, the Third Military Medical University, Chongqing, ChinaDepartment of Neurology, Xinqiao Hospital, the Third Military Medical University, Chongqing, ChinaDepartment of Neurology, Xinqiao Hospital, the Third Military Medical University, Chongqing, ChinaDepartment of Neurology, Xinqiao Hospital, the Third Military Medical University, Chongqing, ChinaBasic Medical College, Zhengzhou University, Zhengzhou, ChinaDepartment of Neurology, Key Laboratory of Neurorepair and Regeneration, Tianjin and Ministry of Education, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of Anesthesiology/Critical Care Medicine, School of Medicine, Johns Hopkins University, Baltimore, MDDepartment of Neurology, Xinqiao Hospital, the Third Military Medical University, Chongqing, ChinaBackgroundNeuroinflammation plays a key role in intracerebral hemorrhage (ICH)–induced secondary brain injury, but the specific roles of peripheral inflammatory cells such as macrophages and lymphocytes remain unknown. The purpose of this study was to explore the roles of macrophages, T lymphocytes, and the cytokines they secrete as potential targets for treating secondary brain injury after ICH. Methods and ResultsOur results showed that peripheral macrophages and T lymphocytes successively infiltrated the brain, with macrophage counts peaking 1 day after ICH and T‐lymphocyte counts peaking after 4 days. These peaks in cellular infiltration corresponded to increases in interleukin (IL)‐23 and IL‐17 expression, respectively. We found that hemoglobin from the hematoma activated IL‐23 secretion by infiltrating macrophages by inducing the formation of toll‐like receptor (TLR) 2/4 heterodimer. This increased IL‐23 expression stimulated γδT‐cell production of IL‐17, which increased brain edema and neurologic deficits in the model mice as a proinflammatory factor. Finally, we found that sparstolonin B (SsnB) could ameliorate brain edema and neurologic deficits in ICH model mice via inhibition of TLR2/TLR4 heterodimer formation, and notably, SsnB interacted with myeloid differentiation factor 88 Arg196. ConclusionsTogether, our results reveal the importance of the IL‐23/IL‐17 inflammatory axis in secondary brain injury after ICH and thus provide a new therapeutic target for ICH treatment.https://www.ahajournals.org/doi/10.1161/JAHA.116.004340IL‐17IL‐23intracerebral hemorrhagelymphocytemacrophageTLR2 |
| spellingShingle | Qi Zhong Kai Zhou Qiao‐Li Liang Sen Lin Yan‐Chun Wang Xiao‐Yi Xiong Zhao‐You Meng Ting Zhao Wen‐Yao Zhu Yuan‐Rui Yang Mao‐Fan Liao Qiu‐Wen Gong Liang Liu Ao Xiong Junwei Hao Jian Wang Qing‐Wu Yang Interleukin‐23 Secreted by Activated Macrophages Drives γδT Cell Production of Interleukin‐17 to Aggravate Secondary Injury After Intracerebral Hemorrhage Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease IL‐17 IL‐23 intracerebral hemorrhage lymphocyte macrophage TLR2 |
| title | Interleukin‐23 Secreted by Activated Macrophages Drives γδT Cell Production of Interleukin‐17 to Aggravate Secondary Injury After Intracerebral Hemorrhage |
| title_full | Interleukin‐23 Secreted by Activated Macrophages Drives γδT Cell Production of Interleukin‐17 to Aggravate Secondary Injury After Intracerebral Hemorrhage |
| title_fullStr | Interleukin‐23 Secreted by Activated Macrophages Drives γδT Cell Production of Interleukin‐17 to Aggravate Secondary Injury After Intracerebral Hemorrhage |
| title_full_unstemmed | Interleukin‐23 Secreted by Activated Macrophages Drives γδT Cell Production of Interleukin‐17 to Aggravate Secondary Injury After Intracerebral Hemorrhage |
| title_short | Interleukin‐23 Secreted by Activated Macrophages Drives γδT Cell Production of Interleukin‐17 to Aggravate Secondary Injury After Intracerebral Hemorrhage |
| title_sort | interleukin 23 secreted by activated macrophages drives γδt cell production of interleukin 17 to aggravate secondary injury after intracerebral hemorrhage |
| topic | IL‐17 IL‐23 intracerebral hemorrhage lymphocyte macrophage TLR2 |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.116.004340 |
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