Beta2-adrenergic receptor signaling in CD4(+) Foxp3(+) regulatory T cells enhances their suppressive function in a PKA-dependent manner

Beta2-adrenergic receptor (B2AR) signaling is known to impair Th1-cell differentiation and function in a cAMP-dependent way, leading to inhibition of cell proliferation and decreased production of IL-2 and IFN-. CD4+ Foxp3+ Treg cells play a key role in the regulation of immune responses and are ess...

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Detalles Bibliográficos
Autores: Guereschi, Marcia Grando [UNIFESP], Araujo, Leandro Pires [UNIFESP], Maricato, Juliana Terzi [UNIFESP], Takenaka, Maisa Carla [UNIFESP], Nascimento, Vanessa de Mendonça [UNIFESP], Vivanco, Bruno Camolese [UNIFESP], Reis, Vanessa Oliveira dos [UNIFESP], Keller, Alexandre de Castro [UNIFESP], Brum, Patricia C., Basso, Alexandre Salgado [UNIFESP]
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2013
País:Brasil
Institución:Universidade Federal de São Paulo (UNIFESP)
Repositorio:Repositório Institucional da UNIFESP
Idioma:inglés
OAI Identifier:oai:repositorio.unifesp.br:11600/36106
Acceso en línea:http://dx.doi.org/10.1002/eji.201243005
http://repositorio.unifesp.br/handle/11600/36106
Access Level:acceso abierto
Palabra clave:Foxp3
Noradrenaline
Sympathetic nervous system
Treg cell
Descripción
Sumario:Beta2-adrenergic receptor (B2AR) signaling is known to impair Th1-cell differentiation and function in a cAMP-dependent way, leading to inhibition of cell proliferation and decreased production of IL-2 and IFN-. CD4+ Foxp3+ Treg cells play a key role in the regulation of immune responses and are essential for maintenance of self-tolerance. Nevertheless, very little is known about adrenergic receptor expression in Treg cells or the influence of noradrenaline on their function. Here we show that Foxp3+ Treg cells express functional B2AR. B2AR activation in Treg cells leads to increased intracellular cAMP levels and to protein kinase A (PKA)-dependent CREB phosphorylation. We also found that signaling via B2AR enhances the in vitro suppressive activity of Treg cells. B2AR-mediated increase in Treg-cell suppressive function was associated with decreased IL-2 mRNA levels in responder CD4+ T cells and improved Treg-cell-induced conversion of CD4+ Foxp3 cells into Foxp3+ induced Treg cells. Moreover, B2AR signaling increased CTLA-4 expression in Treg cells in a PKA-dependent way. Finally, we found that PKA inhibition totally prevented the B2AR-mediated increase in Treg-cell suppressive function. Our data suggest that sympathetic fibers are able to regulate Treg-cell suppressive activity in a positive manner through B2AR signaling.

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