Bu–Shen–Yi–Qi formula impairs cytotoxicity of NK cells by up-regulating IDO expression in trophoblasts

Abstract

Recurrent spontaneous abortion (RSA) is a common health problem that affects about 5% of fertile women, when it occurs for unknown reasons, it is called unexplained recurrent spontaneous abortion (URSA). Traditional Chinese medicine, such as Bu–Shen–Yi–Qi formula which consists of Dangshen, Tusizi, Baizhu, Baishuo, Duzhong, Sangjisheng, Sugeng, and Tiaohuangqin, has played an invaluable role in the treatment of RSA since ancient times. However, the mechanism of how it takes effect is still not clear. To identify Bu–Shen–Yi–Qi formula could modulate immune condition at maternal-fetal interface via its effect on trophoblasts, HTR-8 of different treatment were co-cultured with peripheral or decidual natural killer (NK) cells, and the receptors such as NKP30 and NKP46 expression on NK cells were measured by flow cytometry (FCM). In this study, we found that herb medium could increase the IDO expression at appropriate concentrations. As an inhibitor of IDO, 1-MT could impair the inhibitory function of trophoblasts on NK cells. Furthermore, Bu–Shen–Yi–Qi formula could enhance the inhibitory function of trophoblasts on NK cells. In conclusion, Bu–Shen–Yi–Qi formula can inhibit NK cytotoxicity by up-regulating IDO expression in trophoblasts and play a role in the treatment of URSA patients.

Chinese abstract

补肾益气方剂通过上调滋养细胞中IDO的表达来损害NK细胞的细胞毒性。

摘要

反复自然流产（RSA）是一种常见的健康问题, 影响约5％的育龄女性, 当其发生原因不明时, 称为不明原因复发性自然流产（URSA）。补肾益气方剂构成成分为：党参、菟丝子, 白术, 白芍, 杜仲, 桑寄生, 苏梗, 条黄芩, 从古代开始补肾益气方剂在RSA的治疗中就发挥了不可估量的作用。然而, 它的作用机制仍不清楚。为了证实补肾益气方剂可通过作用于滋养细胞来调节母胎界面的免疫状态, 我们将不同处理的HTR-8与外周或蜕膜天然杀伤（NK）细胞共培养, 然后通过流式细胞术（FCM）检测NK细胞上NKP30和NKP46的表达。在这项研究中, 我们发现适当浓度的中草药培养基可以增加IDO表达。作为IDO的抑制剂, 1-MT可损害滋养细胞对NK细胞的抑制作用。 此外, 补肾益气方可增强滋养细胞对NK细胞的抑制作用。总之, 补肾益气通过上调滋养细胞中IDO的表达来抑制NK细胞毒性, 并在URSA患者的治疗中发挥作用。

关键词: 补肾益气方剂, NK细胞, IDO, 滋养细胞, 自然流产

Keywords:

• Bu–Shen–Yi–Qi formula
• NK cells
• IDO
• trophoblasts
• spontaneous abortion

Disclosure statement

The authors declare that they have no conflicts of interest.

Additional information

Funding

This study was supported by the National Natural Science Foundation of China NSFC [No.81373868] to Hai-Yan Wang; the NSFC [No. 31671200, No. 91542108, No. 81471513], the Shanghai Rising-Star Program [16QA1400800], the Development Fund of Shanghai Talents [201557] and the Program for Zhuoxue of Fudan University to Ming-Qing Li.