Inflammatory effects of ex vivo human Th17 cells are suppressed by regulatory T cells.
J Immunol
; 185(6): 3199-208, 2010 Sep 15.
Article
em En
| MEDLINE
| ID: mdl-20720207
Th17 cells are proinflammatory cells associated with many immune-mediated diseases. Major factors limiting the study of human Th17 cells are the lack of an accepted method for their in vitro differentiation or for isolation of a homogenous population of Th17 cells that do not cosecrete IFN-gamma. To overcome these hurdles, we established a novel method to isolate in vivo differentiated Th17 cells from peripheral blood by sorting CD161(+)CCR4(+)CCR6(+)CXCR3(-)CD4(+) T cells. The resulting cells produce high levels of IL-17 but not IFN-gamma, express high levels of retinoic acid-related orphan receptor variant 2, and maintain this phenotype upon expansion. Ex vivo Th17 cells exhibit a low cytotoxic potential and are hyporesponsive to polyclonal anti-CD3/anti-CD28 stimulation. Importantly, ex vivo Th17 cells were susceptible to suppression by both naive and memory regulatory T cells (Tregs), which inhibited production of IL-17, IL-22, and CXCL8. Moreover, Tregs suppressed the antifibrotic effects of Th17 cells in a wound-healing model. These findings provide new tools for the study of normal and pathological functions of bona fide Th17 cells in humans. They also provide new insight into the cross-talk between Th17 cells and immune and nonimmune cells, and they establish the paradigm that adoptive Treg-based therapies may effectively limit Th17-mediated inflammation.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Regulação para Baixo
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Linfócitos T Reguladores
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Linfócitos T Auxiliares-Indutores
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Mediadores da Inflamação
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Interleucina-17
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article