Cerebral regulatory T cells restrain microglia/macrophage-mediated inflammatory responses via IL-10

Luokun Xie, Gourav Roy Choudhury, Ali Winters, Shaohua Yang, Kunlin Jin

Research output: Contribution to journalArticleResearchpeer-review

41 Citations (Scopus)

Abstract

Forkhead box P3 (Foxp3)+ regulatory T (Treg) cells maintain the immune tolerance and prevent inflammatory responses in the periphery. However, the presence of Treg cells in the CNS under steady state has not been studied. Here, for the first time, we show a substantial TCRαβ +CD4+Foxp3+ T-cell population (cerebral Treg cells) in the rat cerebrum, constituting more than 15% of the cerebral CD4+ T-cell compartment. Cerebral Treg cells showed an activated/memory phenotype and expressed many Treg-cell signature genes at higher levels than peripheral Treg cells. Consistent with their activated/memory phenotype, cerebral Treg cells robustly restrained the LPS-induced inflammatory responses of brain microglia/macrophages, suggesting a role in maintaining the cerebral homeostasis by inhibiting the neuroinflammation. In addition, brain astrocytes were the helper cells that sustained Foxp3 expression in Treg cells through IL-2/STAT5 signaling, showing that the interaction between astrocytes and Treg cells contributes to the maintenance of Treg-cell identity in the brain. Taken together, our work represents the first study to characterize the phenotypic and functional features of Treg cells in the rat cerebrum. Our data have provided a novel insight for the contribution of Treg cells to the immunosurveillance and immunomodulation in the cerebrum under steady state.

Original languageEnglish
Pages (from-to)180-191
Number of pages12
JournalEuropean Journal of Immunology
Volume45
Issue number1
DOIs
StatePublished - 1 Jan 2015

Fingerprint

Microglia
Regulatory T-Lymphocytes
Interleukin-10
Macrophages
Cerebrum
Astrocytes
Brain
T-Lymphocytes
Phenotype
Immunologic Monitoring
Immune Tolerance
Immunomodulation
Helper-Inducer T-Lymphocytes
Interleukin-2
Homeostasis
Maintenance

Keywords

  • Cerebrum
  • Inflammation
  • Macrophages
  • Microglia
  • Treg

Cite this

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abstract = "Forkhead box P3 (Foxp3)+ regulatory T (Treg) cells maintain the immune tolerance and prevent inflammatory responses in the periphery. However, the presence of Treg cells in the CNS under steady state has not been studied. Here, for the first time, we show a substantial TCRαβ +CD4+Foxp3+ T-cell population (cerebral Treg cells) in the rat cerebrum, constituting more than 15{\%} of the cerebral CD4+ T-cell compartment. Cerebral Treg cells showed an activated/memory phenotype and expressed many Treg-cell signature genes at higher levels than peripheral Treg cells. Consistent with their activated/memory phenotype, cerebral Treg cells robustly restrained the LPS-induced inflammatory responses of brain microglia/macrophages, suggesting a role in maintaining the cerebral homeostasis by inhibiting the neuroinflammation. In addition, brain astrocytes were the helper cells that sustained Foxp3 expression in Treg cells through IL-2/STAT5 signaling, showing that the interaction between astrocytes and Treg cells contributes to the maintenance of Treg-cell identity in the brain. Taken together, our work represents the first study to characterize the phenotypic and functional features of Treg cells in the rat cerebrum. Our data have provided a novel insight for the contribution of Treg cells to the immunosurveillance and immunomodulation in the cerebrum under steady state.",
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Cerebral regulatory T cells restrain microglia/macrophage-mediated inflammatory responses via IL-10. / Xie, Luokun; Choudhury, Gourav Roy; Winters, Ali; Yang, Shaohua; Jin, Kunlin.

In: European Journal of Immunology, Vol. 45, No. 1, 01.01.2015, p. 180-191.

Research output: Contribution to journalArticleResearchpeer-review

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