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

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 central nervous system 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 normal 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 normal 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.

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

“…In agreement with our results, Tregs modulated the function of macrophages through IL-4, IL-10, and IL-13, but not TGF-b. 34,35 Furthermore, previous reports have indicated that PI3K/Akt signaling is responsible for macrophage polarization, and GSK3b/ PTEN lies up-stream of PI3K/Akt. 37,45 Our results also indicate that Tregs can reverse the hemoglobininduced reduction in GSK3b in microglia and subsequently reverse the decrease in P-PTEN.…”

Phenotypical characterization of regulatory T cells in humans and rodents

“…In rats, T reg phenotypes have been less studied; we have observed that approximately 20% of CD4 T regs was observed [80].…”

Phenotype and function of tissue-resident unconventional Foxp3-expressing CD4+ regulatory T cells

“…In the rat cerebrum, a substantial of Treg cells with activated/memory phenotype (TCRab + CD4 + Foxp3 + CD44H + CD62L À Treg cells) are identified, and these Treg cells also express higher levels of other activation/memory markers including ICOS, CD103, KLRG1 and CTLA-4 [66]. Studies in cerebrospinal fluid of human support the idea that T cells in the CNS are mainly activated/memory phenotype [67].…”

“…Studies in cerebrospinal fluid of human support the idea that T cells in the CNS are mainly activated/memory phenotype [67]. Cerebral Treg cells in rats constitute more than 15% of the cerebral CD4 + T cell compartment [66]. Notably, brain astrocytes may have a regulatory role in the control of cerebral Treg cells, because brain astrocytes contribute to Foxp3 expression in Treg cells through IL-2/STAT5 signaling [66].…”