| Autor: |
Marcia G, Guereschi, Leandro P, Araujo, Juliana T, Maricato, Maisa C, Takenaka, Vanessa M, Nascimento, Bruno C, Vivanco, Vanessa O, Reis, Alexandre C, Keller, Patrícia C, Brum, Alexandre S, Basso |
| Rok vydání: |
2012 |
| Předmět: |
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| Zdroj: |
European journal of immunology. 43(4) |
| ISSN: |
1521-4141 |
| Popis: |
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-γ. 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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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