Pharmacological blockade of α1-adrenoceptor is shown to influence development of experimental autoimmune encephalomyelitis (EAE), an IL-17-producing CD4+TCR+ (Th17) cell-mediated disease mimicking multiple sclerosis. Considering significance of CD4+ cell priming for the clinical outcome of EAE, the study examined α1-adrenoceptor-mediated influence of catecholamines, particularly those derived from draining lymph node (dLN) cells (as catecholamine supply from nerve fibers decreases with the initiation of autoimmune diseases) for CD4+ cell priming. The results confirmed diminishing effect of immunization on nerve fiber-derived noradrenaline supply and showed that antigen presenting and CD4+ cells synthesize catecholamines, while antigen presenting cells and only CD4+CD25+Foxp3+ regulatory T cells (Tregs) express α1-adrenoceptor. The analysis of influence of α1-adrenoceptor antagonist prazosin on the myelin basic protein (MBP)-stimulated CD4+ lymphocytes in dLN cell culture showed their diminished proliferation in the presence of prazosin. This was consistent with prazosin enhancing effect on Treg frequency and their Foxp3 expression in these cultures. The latter was associated with upregulation of TGF-β expression. Additionally, prazosin decreased antigen presenting cell activation and affected their cytokine profile by diminishing the frequency of cells that produce Th17 polarizing cytokines (IL-1β and IL-23) and increasing that of IL-10-producing cells. Consistently, the frequency of all IL-17A+ cells and those co-expressing GM-CSF within CD4+ lymphocytes was decreased in prazosin-supplemented MBP-stimulated dLN cell cultures. Collectively, the results indicated that dLN cell-derived catecholamines may influence EAE development by modulating interactions between distinct subtypes of CD4+ T cells and antigen presenting cells through α1-adrenoceptor and consequently CD4+ T cell priming.

中文翻译：

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去甲肾上腺素调节大鼠实验性自身免疫性脑脊髓炎的CD4 + T细胞启动：α1-肾上腺素受体的作用。

研究表明，α1-肾上腺素受体的药理学阻断作用会影响实验性自身免疫性脑脊髓炎（EAE）的发展，EAE是一种产生IL-17的CD4 + TCR +（Th17）细胞介导的模仿多发性硬化症的疾病。考虑到CD4 +细胞启动对EAE临床结局的重要性，该研究检查了α1肾上腺素受体介导的儿茶酚胺的影响，特别是那些源自引流淋巴结（dLN）细胞的影响（因为随着自身免疫性疾病的发作，神经纤维中的儿茶酚胺供应减少）用于CD4 +细胞启动。该结果证实了免疫对神经纤维来源的去甲肾上腺素供应的减弱作用，并表明抗原呈递和CD4 +细胞合成儿茶酚胺，而抗原呈递细胞和仅CD4 + CD25 + Foxp3 +调节性T细胞（Tregs）表达α1-肾上腺素受体。分析dLN细胞培养中α1-肾上腺素能受体拮抗剂prazosin对髓鞘碱性蛋白（MBP）刺激的CD4 +淋巴细胞的影响，结果表明在存在prazosin的情况下它们的增殖减弱。这与哌唑嗪在这些培养物中对Treg频率及其Foxp3表达的增强作用相一致。后者与TGF-β表达的上调有关。另外，哌唑嗪通过减少产生Th17极化细胞因子的细胞（IL-1β和IL-23）的频率并增加产生IL-10的细胞的频率而降低了抗原呈递细胞的活化并影响了它们的细胞因子谱。一致地，在补充用哌唑嗪的MBP刺激的dLN细胞培养物中，所有IL-17A +细胞和在CD4 +淋巴细胞中共表达GM-CSF的细胞的频率均降低。总的来说，