title: 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 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.
authors.affiliation: Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX, USA.
authors.forename: Luokun
authors.initials: L
authors.lastname: Xie
authors.forename: Gourav Roy
authors.initials: GR
authors.lastname: Choudhury
authors.forename: Ali
authors.initials: A
authors.lastname: Winters
authors.forename: Shao-Hua
authors.initials: SH
authors.lastname: Yang
authors.forename: Kunlin
authors.initials: K
authors.lastname: Jin
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D002450:Cell Communication; D054022:Cerebrum / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D004660:Encephalitis / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D005786:Gene Expression Regulation; D007156:Immunologic Memory; D007157:Immunologic Surveillance; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology*; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D008297:Male; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology* / Q000473:pathology
chemical_list: D007376:Interleukin-2; D008070:Lipopolysaccharides; D050799:STAT5 Transcription Factor; D016753:Interleukin-10
keywords: Cerebrum; Inflammation; Macrophages; Microglia; Treg