Beta2 adrenergic receptor signaling in CD4+ Foxp3+ regulatory T cells enhances their suppressive function in vitro
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1
Universidade Federal de São Paulo, Microbiology, Immunology and Parasitology, Brazil
Beta2 adrenergic receptor (B2AR) signaling is known to impair Th1-cell differentiation and function in a cAMP-dependent way. Foxp3+CD4+regulatory T (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. We showed by qPCR, immunofluorescence and western blot that sorted Foxp3+ Treg cells express B2AR. B2AR activation by specific agonist in Treg cells leads to increased intracellular cAMP levels and to PKA-dependent
CREB phosphorylation. For suppression assays, sorted naïve T cells and Treg cells were cultured (proportion 1:0,25) with irradiated splenocytes and soluble anti-CD3. Before setting up the cultures, Treg cells were treated or not with B2AR agonist. After 3 days, naïve T cell proliferation was analyzed by flow cytometry. We found that B2AR signaling enhances the suppressive activity of Treg cells since naïve T cell proliferation was about 40% lower than the one observed in control cultures. 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+ iTreg 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.
Financial support: FAPESP, CNPq
Keywords:
B2 adrenergic receptor,
Treg cells,
Foxp3,
PKA signaling,
CD4 lymphocyte,
noradrenaline
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Adaptive Immunity
Citation:
Guereschi
MG,
Araujo
LP,
Maricato
JT,
Takenaka
MC,
Nascimento
VM,
Vivanco
BC,
Reis
VO,
Keller
AD and
Basso
AS
(2013). Beta2 adrenergic receptor signaling in CD4+ Foxp3+ regulatory T cells enhances their suppressive function in vitro.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.01032
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Received:
29 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Marcia G Guereschi, Universidade Federal de São Paulo, Microbiology, Immunology and Parasitology, São Paulo, Sâo Paulo, 04023-900, Brazil, mgueres@yahoo.com.br