Department of Allergology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland.
J Biol Regul Homeost Agents. 2013 Apr-Jun;27(2):427-42.
Signaling through interleukin-7 receptor (IL-7R) is essential for regulation of T-cell homeostasis and survival. Previously, we and others have found diminished IL-7R levels in simian immunodeficiency virus (SIV) - infected non-human primates and human immunodeficiency virus (HIV) - infected patients. To date, it remains unknown whether changes in IL-7R expression could also be linked to non-infectious inflammatory diseases such as asthma or anti-inflammatory drug use. Here, we investigated through flow cytometry the levels of IL-7R expression on CD4+ and CD4- T-cells in asthmatic patients in relation to disease severity, immune status and glucocorticoid (GC) use. In addition, we sought to evaluate the effects of in vivo and in vitro GC treatment on IL-7R expression in both asthmatic patients and SIV-infected non-human primates. We demonstrated that expression of IL-7R on peripheral blood CD4+ T-cells was significantly decreased in clinically stable GC-naive mild and moderate asthmatic patients. Accordingly, the development of asthmatic reaction following bronchial allergen challenge performed in sensitized subjects was associated with a significant drop in levels of IL-7R on circulating CD4+ T-cells. In contrast, CD4+ T-cells from both, mild and moderate, but not severe asthmatics, treated with inhaled GC displayed levels of IL-7R similar to that seen in healthy controls. We did not find significant differences with serum or sputum interleukin-7 levels among healthy controls and GC-naïve and GC-treated asthmatic patients. Furthermore, both in vitro GC treatment and short-term oral GC administration to asthmatic patients resulted in a significant enhancement of IL-7R. Similarly, we demonstrated that GC-stimulated T-cells from SIV-infected non-human primates up-regulated IL-7R expression. Accordingly, experimental short-term systemic in vivo administration of GC to SIV-infected macaques led to enhancement of IL-7R expression on circulating T-cells. Our data indicate that GC bear potential to recover diminished IL-7R expression, as well in asthma as in lentiviral infection.
白细胞介素-7 受体（IL-7R）信号对于 T 细胞的稳态和存活的调节至关重要。此前，我们和其他人已经发现，在感染了猴免疫缺陷病毒（SIV）的非人类灵长类动物和感染了人类免疫缺陷病毒（HIV）的患者中，IL-7R 水平降低。迄今为止，尚不清楚 IL-7R 表达的变化是否也与非传染性炎症性疾病（如哮喘或抗炎药物的使用）有关。在这里，我们通过流式细胞术研究了哮喘患者中 CD4+和 CD4- T 细胞上 IL-7R 表达水平与疾病严重程度、免疫状态和糖皮质激素（GC）使用之间的关系。此外，我们试图评估体内和体外 GC 治疗对哮喘患者和 SIV 感染的非人类灵长类动物中 IL-7R 表达的影响。我们证明，在临床稳定、GC 治疗初治的轻度和中度哮喘患者中，外周血 CD4+T 细胞上 IL-7R 的表达显著降低。因此，在致敏患者中进行支气管变应原激发后，哮喘反应的发展与循环 CD4+T 细胞上 IL-7R 水平的显著下降有关。相比之下，来自轻度和中度哮喘患者的 CD4+T 细胞，但不是来自重度哮喘患者的 CD4+T 细胞，经吸入 GC 治疗后，IL-7R 水平与健康对照组相似。我们没有发现健康对照组和 GC 初治和 GC 治疗的哮喘患者之间血清或痰白细胞介素-7 水平有显著差异。此外，体外 GC 治疗和短期口服 GC 给药均可导致哮喘患者的 IL-7R 显著增强。同样，我们证明了 SIV 感染的非人类灵长类动物中的 GC 刺激 T 细胞上调了 IL-7R 的表达。因此，实验性短期全身体内给予 GC 可增强循环 T 细胞上的 IL-7R 表达。我们的数据表明，GC 具有恢复减弱的 IL-7R 表达的潜力，无论是在哮喘还是在慢病毒感染中。
