芳香烃受体调控人脂肪间充质干细胞的免疫调节功能

doi:10.16352/j.issn.1001-6325.2023.06.0889

基础医学与临床 ›› 2023, Vol. 43 ›› Issue (6): 889-897.doi: 10.16352/j.issn.1001-6325.2023.06.0889

芳香烃受体调控人脂肪间充质干细胞的免疫调节功能

武文婧¹, 高竞溪¹, 赵晓妍¹, 孙昭², 韩钦^1*, 赵春华^1*

1.中国医学科学院基础医学研究所北京协和医学院基础学院中国医学科学院组织工程研究中心,北京 100005;
2.中国医学科学院北京协和医学院北京协和医院肿瘤内科,北京 100730

收稿日期:2023-03-24 修回日期:2023-04-19 出版日期:2023-06-05 发布日期:2023-05-31
通讯作者: ^*hanqinhanqin@126.com; zhaochunhua@ibms.pumc.edu.cn
基金资助:
中国医学科学院医学与健康科技创新工程(2022-I2M-1-012,2021-I2M-1-051);国家自然科学基金(81971324,81902848)

AHR regulates the immunomodulatory function of human adipose-derived mesenchymal stem cells

WU Wenjing¹, GAO Jingxi¹, ZHAO Xiaoyan¹, SUN Zhao², HAN Qin^1*, ZHAO Chunhua^1*

1. Center for Excellence in Tissue Engineering,Chinese Academy of Medical Sciences, Institute of Basic Medical Sciences CAMS, School of Basic Medicine PUMC, Beijing 100005;
2. Department of Oncology, Peking Union Medical College Hospital, CAMS & PUMC,Beijing 100730, China

Received:2023-03-24 Revised:2023-04-19 Online:2023-06-05 Published:2023-05-31
Contact: ^*hanqinhanqin@126.com; zhaochunhua@ibms.pumc.edu.cn

摘要/Abstract

摘要： 目的探索芳香烃受体(AHR)对人脂肪间充质干细胞(MSCs)免疫调节功能的影响。方法 RT-qPCR和免疫荧光染色法检测炎性细胞因子刺激前后,MSCs中吲哚胺2,3-双加氧酶1(IDO1)、白细胞介素-4诱导基因1(IL4I1)和芳香烃受体表达水平;将si-Ctrl、si-IDO1、si-IL4I1、si-AHR转染至MSCs,阻断AHR信号通路;将MSCs的条件培养基与巨噬细胞共培养,RT-qPCR和ELISA检测巨噬细胞炎性因子IL-6、IL-1β、TNF-α水平。结果未经细胞因子刺激的MSCs高表达AHR,几乎不表达IDO和IL4I1蛋白;不同细胞因子刺激后,代谢酶IDO1、IL4I1及AHR表达上调(P＜0.05),IFN-γ刺激后IDO1、IL4I1表达上调最为显著(P＜0.001),进入细胞核的AHR增多;下调AHR的表达削弱MSCs的免疫抑制作用(P＜0.05)。结论 AHR参与调节MSCs的免疫功能,下调AHR可以抑制MSCs的免疫调节作用。

关键词: 芳香烃受体, 间充质干细胞, 免疫调节作用

Abstract: Objective To explore the effect of aryl hydrocarbon receptor(AHR) on the immunomodulatory function of human adipose derived mesenchymal stem cells (MSCs). Methods RT-qPCR and immunofluorescence staining were used to detect the expression levels of indoleamine 2,3-dioxygenase 1 (IDO1), interleukin-4-inducible gene 1 (IL4I1) and AHR in MSCs before and after inflammatory cytokine stimulation; siCtrl, siIDO1, siIL4I1 and siAHR were transfected into MSCs and blocked the AHR signaling pathway; conditioned medium from MSCs was co-incubated with macrophages, RT-qPCR and ELISA were performed to detect the level of IL-6, IL-1β, TNF-α. Results MSCs without cytokine stimulation highly expressed AHR and hardly expressed IDO1 and IL4I1 proteins; IDO1, IL4I1 and AHR were up-regulated after different cytokine stimulation(P＜0.05), the expression of IDO1 and IL4I1 was most significantly up-regulated after stimulation by IFN-γ(P＜0.001), AHR entering the nucleus was increased; down-regulation of AHR expression could inhibit the immunomodulatory effect of MSCs(P＜0.05). Conclusions AHR regulates the immune function of MSCs, downregulates expression of AHR could inhibit the immunomodulatory effects of MSCs.

Key words: aryl hydrocarbon receptor(AHR), mesenchymal stem cells, immunomodulatory effects

中图分类号:

Q291

武文婧, 高竞溪, 赵晓妍, 孙昭, 韩钦, 赵春华. 芳香烃受体调控人脂肪间充质干细胞的免疫调节功能[J]. 基础医学与临床, 2023, 43(6): 889-897.

WU Wenjing, GAO Jingxi, ZHAO Xiaoyan, SUN Zhao, HAN Qin, ZHAO Chunhua. AHR regulates the immunomodulatory function of human adipose-derived mesenchymal stem cells[J]. Basic & Clinical Medicine, 2023, 43(6): 889-897.

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芳香烃受体调控人脂肪间充质干细胞的免疫调节功能

AHR regulates the immunomodulatory function of human adipose-derived mesenchymal stem cells

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