Interleukin-23 secreted by activated macrophages drives γδT cell production of interleukin-17 to aggravate secondary injury after intracerebral hemorrhage

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

Research output: Contribution to journalArticlepeer-review

Abstract

Background-Neuroinflammation 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 Results-Our 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. Conclusions-Together, 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.

Original languageEnglish (US)
Article numbere004340
JournalJournal of the American Heart Association
Volume5
Issue number10
DOIs
StatePublished - Oct 1 2016

Keywords

  • IL-17
  • IL-23
  • Intracerebral hemorrhage
  • Lymphocyte
  • Macrophage
  • TLR2
  • TLR4

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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