Langerhans cells β2-adrenoceptors: role in migration, cytokine production, Th priming and contact hypersensitivity

Abstract

We showed that norepinephrine (NE) hampers IL-12 and stimulates IL-10 production via adrenoceptors (ARs) in bone marrow-derived dendritic cells (BMDC) influencing their Th priming ability. Others have shown that Langerhans cells (LC) express mRNA for β1-, β2- and α1 A-(ARs) and that catecholamines may inhibit the antigen-presenting capability via β2-ARs. Here, we show that also BMDC express mRNA for β1-, β2-, α2 A- and α2 C-ARs. Inhibition of IL-12 is mediated by both β2- and α2 A-ARs, while stimulation of IL-10 by β2-ARs only. In addition, LC migration, the contact hypersensitivity response (CHS) and production of IFN-γ and IL-2 in draining lymph node cells is increased in mice treated topically with the β2-AR antagonist ICI 118,551 during FITC sensitization. Activation of β2-ARs in BMDC before adoptive transfer could reduce both migration and CHS response to FITC. Finally, preincubation of BMDC with LPS in presence of the specific β2-AR agonist salbutamol impaired their chemotactic response to CCL19 and CCL21 and this effect was neutralized by anti-IL-10 mAb. We suggest that the physiological activation of β2-ARs in DC (LC) results in stimulation of IL-10 which in turn restrains DC (LC) migration influencing antigen presentation and the consequent CHS response.