Pathogen-induced human TH17 cells produce IFN-γ or IL-10 and are regulated by IL-1ß.
Nature
; 484(7395): 514-8, 2012 Apr 26.
Article
en En
| MEDLINE
| ID: mdl-22466287
ABSTRACT
IL-17-producing CD4+ T helper cells (TH17) have been extensively investigated in mouse models of autoimmunity. However, the requirements for differentiation and the properties of pathogen-induced human TH17 cells remain poorly defined. Using an approach that combines the in vitro priming of naive T cells with the ex vivo analysis of memory T cells, we describe here two types of human TH17 cells with distinct effector function and differentiation requirements. Candida albicans-specific TH17 cells produced IL-17 and IFN-γ, but no IL-10, whereas Staphylococcus aureus-specific TH17 cells produced IL-17 and could produce IL-10 upon restimulation. IL-6, IL-23 and IL-1ß contributed to TH17 differentiation induced by both pathogens, but IL-1ß was essential in C. albicans-induced TH17 differentiation to counteract the inhibitory activity of IL-12 and to prime IL-17/IFN-γ double-producing cells. In addition, IL-1ß inhibited IL-10 production in differentiating and in memory TH17 cells, whereas blockade of IL-1ß in vivo led to increased IL-10 production by memory TH17 cells. We also show that, after restimulation, TH17 cells transiently downregulated IL-17 production through a mechanism that involved IL-2-induced activation of STAT5 and decreased expression of ROR-γt. Taken together these findings demonstrate that by eliciting different cytokines C. albicans and S. aureus prime TH17 cells that produce either IFN-γ or IL-10, and identify IL-1ß and IL-2 as pro- and anti-inflammatory regulators of TH17 cells both at priming and in the effector phase.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Staphylococcus aureus
/
Candida albicans
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Interferón gamma
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Interleucina-10
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Interleucina-1beta
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Células Th17
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Nature
Año:
2012
Tipo del documento:
Article
País de afiliación:
Suiza