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

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

Autor Guereschi, Marcia Grando Autor UNIFESP Google Scholar
Araujo, Leandro Pires Autor UNIFESP Google Scholar
Maricato, Juliana Terzi Autor UNIFESP Google Scholar
Takenaka, Maisa Carla Autor UNIFESP Google Scholar
Nascimento, Vanessa de Mendonça Autor UNIFESP Google Scholar
Vivanco, Bruno Camolese Autor UNIFESP Google Scholar
Reis, Vanessa Oliveira dos Autor UNIFESP Google Scholar
Keller, Alexandre de Castro Autor UNIFESP Google Scholar
Brum, Patricia C. Google Scholar
Basso, Alexandre Salgado Autor UNIFESP Google Scholar
Instituição Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Resumo 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.
Palavra-chave Foxp3
Noradrenaline
Sympathetic nervous system
Treg cell
Idioma Inglês
Financiador Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Número do financiamento FAPESP: 08/58564-9
FAPESP: 09/51886-3
CNPq: 475000/2010-2
Data de publicação 2013-04-01
Publicado em European Journal of Immunology. Hoboken: Wiley-Blackwell, v. 43, n. 4, p. 1001-1012, 2013.
ISSN 0014-2980 (Sherpa/Romeo, fator de impacto)
Publicador Wiley-Blackwell
Extensão 1001-1012
Fonte http://dx.doi.org/10.1002/eji.201243005
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000317859200017
Endereço permanente http://repositorio.unifesp.br/handle/11600/36106

Exibir registro completo




Arquivo

Arquivo Tamanho Formato Visualização

Não existem arquivos associados a este item.

Este item está nas seguintes coleções

Buscar


Navegar

Minha conta