Medical Clinic III for Oncology, Hematology, Immuno-Oncology and Rheumatology, University Hospital Bonn Sigmund-Freud-Straße 25, 53127, Bonn, Germany.
Sci Rep. 2017 Jul 3;7(1):4522. doi: 10.1038/s41598-017-04558-z.
Treatment of patients with glucocorticoids can result in an increased risk of infection with pathogens such as fungi. Dectin-1 is a member of the C-type lectin receptor superfamily and was shown to be one of the major receptors for fungal beta-glucans. Activation of Dectin-1 increases the production of cytokines and chemokines and T-cell stimulatory capacity of DC and mediates resolution of fungal infections. Here we show that antigen-presenting cells generated in the presence of dexamethasone (Dex-DC) have a reduced capacity to stimulate T-cell proliferation and decreased expression of costimulatory molecules, that can not be enhanced upon stimulation with Dectin-1 ligands. Stimulation of Dex-DC with beta-glucans induced a strong upregulation of Syk phosphorylation and increased secretion of IL-10, while the production of IL-12, IL-23 and TNF-alpha was reduced. Downstream of Syk stimulation of Dectin-1 on Dex-DC resulted in phosphorylation of STAT3 and reduced nuclear localization of transcription factors involved in DC activation and function.
糖皮质激素治疗可使患者感染真菌等病原体的风险增加。Dectin-1 是 C 型凝集素受体超家族的成员之一，被证实是真菌β-葡聚糖的主要受体之一。Dectin-1 的激活可增加细胞因子和趋化因子的产生以及 DC 的 T 细胞刺激能力，并介导真菌感染的消退。在这里，我们表明，在地塞米松（Dex-DC）存在下生成的抗原呈递细胞刺激 T 细胞增殖的能力降低，并且共刺激分子的表达降低，而不能通过 Dectin-1 配体的刺激增强。用β-葡聚糖刺激 Dex-DC 可诱导 Syk 磷酸化的强烈上调，并增加 IL-10 的分泌，而 IL-12、IL-23 和 TNF-α 的产生减少。Dectin-1 对 Dex-DC 的 Syk 刺激的下游导致参与 DC 激活和功能的转录因子的 STAT3 磷酸化和核定位减少。
