New roles for CD14 and IL-ß linking inflammatory dendritic cells to IL-17 production in memory CD4+ T cells.
Immunol Cell Biol
; 94(10): 907-916, 2016 11.
Article
em En
| MEDLINE
| ID: mdl-27550748
ABSTRACT
Interleukin (IL)-1ß has proven to be crucial in the differentiation of human and mouse Th17 cells. Although it has become evident that IL-1ß has potent IL-17-inducing effects on CD4+ T cells directly, it has not yet been explored whether IL-1ß can also prime dendritic cells (DCs) for a Th17 instruction program. Here, we show that human immature DCs exposed to IL-1ß promote IL-17 production in human memory CD4+ T cells. IL-1ß-primed DCs express high levels of CD14 that mediate IL-17 production through direct interaction with T cells. Moreover, culturing human CD4+CD45RO+ memory T cells with soluble CD14 is sufficient for the upregulation of retinoic acid-related orphan receptor-γ thymus and IL-17 production. In addition, in a human in situ model using tissue-resident skin DCs, upregulation of CD14 expression induced by IL-1ß on skin residents DCs promotes IL-17 production in memory T cells; strongly suggesting the in vivo relevance of this mechanism. Our findings uncover new roles for IL-1ß and CD14, and may therefore have important consequences for the development of new therapies for Th17-mediated autoimmune diseases and bacterial and fungal pathogenic infections.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
/
Linfócitos T CD4-Positivos
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Receptores de Lipopolissacarídeos
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Interleucina-17
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Interleucina-1beta
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Memória Imunológica
/
Inflamação
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Immunol Cell Biol
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Holanda