Details

Autor(en) / Beteiligte

• Guereschi, Marcia G.
• Araujo, Leandro P.
• Maricato, Juliana T.
• Takenaka, Maisa C.
• Nascimento, Vanessa M.
• Vivanco, Bruno C.
• Reis, Vanessa O.
• Keller, Alexandre C.
• Brum, Patrícia C.
• Basso, Alexandre S.

Titel

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

Ist Teil von

• European journal of immunology, 2013-04, Vol.43 (4), p.1001-1012

Ort / Verlag

Germany: Wiley Subscription Services, Inc

Erscheinungsjahr

2013

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• 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.