Regulatory T cells ameliorate intracerebral hemorrhage-induced inflammatory injury by modulating microglia/macrophage polarization through the IL-10/GSK3β/PTEN axis

Kai Zhou, Qi Zhong, Yan Chun Wang, Xiao Yi Xiong, Zhao You Meng, Ting Zhao, Wen Yao Zhu, Mao Fan Liao, Li Rong Wu, Yuan Rui Yang, Juan Liu, Chun Mei Duan, Jie Li, Qiu Wen Gong, Liang Liu, Mei Hua Yang, Ao Xiong, Jian Wang, Qing Wu Yang

Research output: Contribution to journalArticle

Abstract

Inflammation mediated by the peripheral infiltration of inflammatory cells plays an important role in intracerebral hemorrhage (ICH) induced secondary injury. Previous studies have indicated that regulatory T lymphocytes (Tregs) might reduce ICH-induced inflammation, but the precise mechanisms that contribute to ICH-induced inflammatory injury remain unclear. Our results show that the number of Tregs in the brain increases after ICH. Inducing Tregs deletion using a CD25 antibody or Foxp3 DTR-mice increased neurological deficient scores (NDS), the level of inflammatory factors, hematoma volumes, and neuronal degeneration. Meanwhile, boosting Tregs using a CD28 super-Agonist antibody reduced the inflammatory injury. Furthermore, Tregs depletion shifted microglia/macrophage polarization toward the M1 phenotype while boosting Tregs shifted this transition toward the M2 phenotype. In vitro, a transwell co-culture model of microglia and Tregs indicated that Tregs changed the polarization of microglia, decreased the expression of MHC-II, IL-6, and TNF-α and increased CD206 expression. IL-10 originating from Tregs mediated the microglia polarization by increasing the expression of Glycogen Synthase Kinase 3 beta (GSK3β), which phosphorylates and inactivates Phosphatase and Tensin homologue (PTEN) in microglia, TGF-β did not participate in this conversion. Thus, Tregs ameliorated ICH-induced inflammatory injury by modulating microglia/macrophage polarization toward the M2 phenotype through the IL-10/GSK3β/PTEN axis.

Original languageEnglish (US)
Pages (from-to)967-979
Number of pages13
JournalJournal of Cerebral Blood Flow and Metabolism
Volume37
Issue number3
DOIs
StatePublished - Mar 1 2017

Keywords

  • inflammation
  • Intracerebral hemorrhage
  • macrophages
  • microglia
  • T-cells

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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  • Cite this

    Zhou, K., Zhong, Q., Wang, Y. C., Xiong, X. Y., Meng, Z. Y., Zhao, T., Zhu, W. Y., Liao, M. F., Wu, L. R., Yang, Y. R., Liu, J., Duan, C. M., Li, J., Gong, Q. W., Liu, L., Yang, M. H., Xiong, A., Wang, J., & Yang, Q. W. (2017). Regulatory T cells ameliorate intracerebral hemorrhage-induced inflammatory injury by modulating microglia/macrophage polarization through the IL-10/GSK3β/PTEN axis. Journal of Cerebral Blood Flow and Metabolism, 37(3), 967-979. https://doi.org/10.1177/0271678X16648712