Up-regulation of EP2 and EP3 receptors in human tolerogenic dendritic cells boosts the immunosuppressive activity of PGE2.
J Leukoc Biol
; 102(3): 881-895, 2017 09.
Article
em En
| MEDLINE
| ID: mdl-28630103
ABSTRACT
Dendritic cells (DCs) are APCs essential in regulating the immune response. PGE2, produced during inflammation, has a pivotal role in the maturation of DCs and, therefore, is vital for the immune response. The large variety of biologic functions governed by PGE2 is mediated by its signaling through 4 distinct E-type prostanoid (EP) receptors. Immunogenic DCs express EP2 and EP4, which mediate the PGE2 signaling. However, the expression and function of EP receptors in human tolerogenic DCs (tol-DCs), which present an inhibitory phenotype, have not yet, to our knowledge, been assessed. To clarify the role of EP receptors in tol-DCs, we examined the expression of different EP receptors and their effect using selective agonists in human cells. We find that EP2 and EP3 expression are up-regulated in in vitro-generated tol-DCs compared with mature DCs (mDCs). Activation of EP2-EP4 has a direct effect on the surface expression of costimulatory molecules and maturation receptors, such as CD80, CD83, and CD86 or MHCII and CCR7 in tol-DCs, the latter being exclusively modulated by PGE2-EP4 signaling. Importantly, we find that EP2 and EP3 receptors are involved in tolerance induction through IL-10 production by tol-DCs. These results are in sharp contrast with the inflammatory role of EP4 Moreover, we show that DCs generated in the presence of agonists for EP receptors, induce naive T cell differentiation toward polarized Th1/Th17 cells. Given the differential effects of EP receptors, our results suggest that EP receptor agonist/antagonists might become relevant novel drug templates to modulate immune response.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
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Dinoprostona
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Receptores de Prostaglandina E Subtipo EP2
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Receptores de Prostaglandina E Subtipo EP3
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Tolerância Imunológica
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Imunossupressores
Limite:
Humans
Idioma:
En
Revista:
J Leukoc Biol
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Espanha