调节性T淋巴细胞转化生长因子-β白细胞介素-17对狼疮肾炎的影响及相互关系

The effect and association of regulatory T cells, transforming growth factor beta, interleukin-17 with lupus nephritis

目的检测活动期、静止期狼疮肾炎（LN）患者及健康人外周血白细胞介素（IL）-10、IL-6、转化生长因子（TGF）-β、IL-17、CD4^＋CD25^＋CD127^lo调节性T淋巴细胞水平，探讨TGF—β与调节性T淋巴细胞、IL-6、IL-17在LN的变化及相互关系。方法采用三色荧光染色通过流式细胞仪（FCM）检测外周血中CD4^＋CD25^＋CD127^lo细胞水平，以双抗体夹心酶联免疫吸附（ELISA）法测定LN患者外周血中TGF—β、IL-17水平，用CBA流式蛋白分析系统检测外周血中IL—10、IL-6水平。结果①活动期LN患者外周血调节性T淋巴细胞低于静止期、健康组（P〈0．01），静止期与健康组差异无统计学意义（P〉0．05）。②活动期LN患者IL-10、IL-6与静止期相比显著升高（P〈0．01）。③活动期LN、静止期LN、健康组TGF—β、IL-17无变化。④LN患者调节性T淋巴细胞与IL-10、IL-6、SLEDAI之间呈负相关（P〈0．05）；与C3、C4之间无显著相关性。⑤LN患者外周血IL-10、IL-6与SLEDAI呈正相关（P〈0．01），与C3、C4均呈负相关（P〈0．01）。LN患者外周血SLEDAI与C3、C4均呈负相关（P〈0．01）。⑥LN患者调节性T淋巴细胞与TGF—β、IL-17之间无相关性。⑦TGF—β与IL-17呈正相关（P〈0．01）。结论①LN患者外周血中调节性T淋巴细胞及IL-10、IL-6、TGF—β的水平变化可作为狼疮活动性的指标。②LN患者外周血中调节性T淋巴细胞与IL-10、IL-6呈负相关。③激素有助于提高调节性T淋巴细胞，降低IL-17。④T淋巴细胞将随机体状态、局部微环境的改变以及维护机体免疫平衡的需要出现不同的极化。

Objective- To explore the role of CD4^＋CD25^＋CD127^lo regulatory T cells （Tregs） and interleukin （IL）-6, transforming growth factor beta （TGF-β）, IL-17 in the pathogenesis of lupus nephritis （LN） by detecting the levels of IL-10, IL-6, TGF-β, IL-17, CD4^＋CD25^＋CD127^lo Tregs in the peripheral blood of patients with active and inactive LN. Methods Three-colour flow cytometry was used to quantitatively measure proportions of Treg cells, the levels of TGF-β, IL-17 were detected by ELISA, and the levels of IL- 10, IL-6 in the peripheral blood were detected by Cytometric Bead Array System. Results （1） Compared with the inactive LN and the normal controls （P〈0.01）, the level of CD4^＋CD25^＋CD127^lo Tregs from patients with active LN was lower（P〈0.01 ）. When compared with the normal controls, the level of CD4^＋CD25^＋CD127^lo Tregs from LN inactive patients had no significant difference （P〉0.05）. （2） Compared with patients with inactive LN, the levels of IL-10, IL-6 was higher （P〈0.01） in patients with active LN. （3） Compared with the patients with inactive LN and the normal controls, the levels of TGF-β, IL-17 was not significantly different （P〉0.05）. （4） The level of CD4^＋CD25^＋CD127^lo T cell was correlated negatively with the levels of IL-10, IL-6 and SLEDAI （P〈0.05）, and was not correlated with C3 and C4. （5） SLEDAI was correlated positively with the levels of IL-10 and IL-6 （P〈0.01）. SLEDAI and the level of IL-10 were correlated negatively with C3 and C4 （P〈0.01 for both）. （6） The level of CD4^＋CD25^＋CD127^lo Tregs from LN was not correlated with TGF-β and IL- 17. （7） TGF-β was correlated positively with the level of IL-17. Conclusion （1） The level changes of Tregs and IL-10, IL-6, TGF-β in the peripheral blood of LN can be used as the indicators for the activity status of lupus nephritis. （2） Tregs and IL-10, IL-6 in the peripheral blood of LN patients is negatively correlated. （3） The glucocorticoid hormone is helpful to elevate the level of Tregs but decrease IL-17. T cell level can vary in different body status, different microenvironmental and immune status.