β2-Adrenoreceptor agonist inhibits antigen cross-presentation by dendritic cells.
2013
HERVE , Julie (INRA , Nantes (France). UMR 0707 Immuno-Endocrinologie Cellulaire et Moléculaire) | Dubreil , Laurence (INRA , Nantes (France). UMR 0703 Physiopathologie animale et biothérapies du muscle et du système nerveux) | Tardif , Virginie (Institut National de la Santé et de la Recherche Médicale, Nantes(France).) | TERME , Mickaël (INRA , Nantes (France). UMR 0707 Immuno-Endocrinologie Cellulaire et Moléculaire) | Pogu , Sylvie (INRA , Nantes (France). UMR 0707 Immuno-Endocrinologie Cellulaire et Moléculaire) | Anegon , Ignacio (Institut National de la Santé et de la Recherche Médicale, Nantes(France).) | Rozec , Bertrand (Institut National de la Santé et de la Recherche Médicale, Nantes(France).) | Gauthier , Chantal | Bach , Jean-Marie (INRA , Nantes (France). UMR 0707 Immuno-Endocrinologie Cellulaire et Moléculaire) | Blancou , Philippe (INRA , Nantes (France). UMR 0707 Immuno-Endocrinologie Cellulaire et Moléculaire)
Despite widespread usage of β-adrenergic receptor (AR) agonists and antagonists in current clinical practice, our understanding of their interactions with the immune system is surprisingly sparse. Among the AR expressed by dendritic cells (DC), β2-AR can modify in vitro cytokine release upon stimulation. Because DC play a pivotal role in CD8(+) T cell immune responses, we examined the effects of β2-AR stimulation on MHC class I exogenous peptide presentation and cross-presentation capacities. We demonstrate that β2-AR agonist-exposed mature DC display a reduced ability to cross-present protein Ags while retaining their exogenous peptide presentation capability. This effect is mediated through the nonclassical inhibitory G (Gαi/0) protein. Moreover, inhibition of cross-presentation is neither due to reduced costimulatory molecule expression nor Ag uptake, but rather to impaired phagosomal Ag degradation. We observed a crosstalk between the TLR4 and β2-AR transduction pathways at the NF-κB level. In vivo, β2-AR agonist treatment of mice inhibits Ag protein cross-presentation to CD8(+) T cells but preserves their exogenous MHC class I peptide presentation capability. These findings may explain some side effects on the immune system associated with stress or β-agonist treatment and pave the way for the development of new immunomodulatory strategies.
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