IECM, Oniris, INRA, Université Bretagne Loire, Nantes, France.
Immunol Res. 2017 Dec;65(6):1156-1163. doi: 10.1007/s12026-017-8966-3.
Adrenergic receptor agonists and antagonists are extensively used as drugs in medicine for a broad spectrum of indications. We examined the consequences of β2-adrenergic stimulation of murine dendritic cells (DCs) on CD4 T cell activation. We demonstrated in vitro that treatment of LPS-matured DCs with the β2-agonist salbutamol reduced their ability to trigger OT-II T cell proliferation specific for ovalbumin antigen. Salbutamol also induced a decrease in MHC class II molecule expression by DC through Gi protein activation. Co-culture of CD4 T cells with salbutamol-conditioned mature DC impaired TNFα and IL-6 secretion while preserving IL-10 production by T cells. Using a vaccination protocol in mice, we showed that salbutamol favored IL-10-producing CD4 T cells. None of these effects was observed when working with β2-adrenoreceptor deficient mice. Finally, we suggest that β2-adrenergic stimulation of DC could be an interesting way to shape CD4 T cell responses for the purposes of immunotherapy.
肾上腺素能受体激动剂和拮抗剂在医学中被广泛用作药物,用于治疗多种适应症。我们研究了β2-肾上腺素能刺激小鼠树突状细胞(DC)对 CD4 T 细胞激活的后果。我们在体外证明,用β2-激动剂沙丁胺醇处理 LPS 成熟的 DC 会降低它们触发针对卵清蛋白抗原的 OT-II T 细胞增殖的能力。沙丁胺醇还通过 Gi 蛋白激活诱导 DC 中 MHC Ⅱ类分子表达下降。与沙丁胺醇调理成熟的 DC 共培养会损害 CD4 T 细胞分泌 TNFα 和 IL-6,同时保持 T 细胞产生 IL-10。在小鼠中使用疫苗接种方案,我们发现沙丁胺醇有利于产生 IL-10 的 CD4 T 细胞。在用缺乏β2-肾上腺素能受体的小鼠进行实验时,没有观察到这些作用。最后,我们认为β2-肾上腺素能刺激 DC 可能是一种调节 CD4 T 细胞反应以进行免疫治疗的有趣方法。