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肿瘤来源的髓源性抑制细胞通过调节白细胞介素-10和白细胞介素-12抑制哮喘小鼠的气道重塑。

Tumor-derived MDSCs inhibit airway remodeling in asthmatic mice through regulating IL-10 and IL-12.

作者信息

Zhang Yanli, Xu Boyi, Luan Bin, Zhang Yan, Wang Xiufang, Xiong Xiaorong, Shi Hongke

机构信息

Department of Pediatrics, The Third Affiliated Hospital of Zhengzhou University Zhengzhou 450052, China.

Institute of Psychology, Chinese Academy of Sciences Beijing 100101, China.

出版信息

Am J Transl Res. 2019 Jul 15;11(7):4192-4202. eCollection 2019.

Abstract

Myeloid-derived suppressor cells (MDSCs), a group of newly discovered and heterogeneous myeloid-derived immunosuppressive cells, play an important role in the progress of asthma, however, the specific mechanism is still largely unclear. Our previous study has indicated that during the onset of asthma, the accumulation of MDSCs and the level of serum interleukin (IL)-10 increased, while the level of IL-12 decreased. The present study aimed to investigate whether tumor-derived MDSCs could inhibit airway remodeling in asthmatic mice through regulating IL-10 and IL-12 secretion. To perform our investigation, we established a mouse model of breast cancer, and the extracted MDSCs from breast caner mouse model were injected into a mouse model of asthma induced by ovalbumin (OVA). Then, asthmatic airway remodeling of mice was analyzed and the levels of IL-10 and IL-12 in the serum and bronchoalveolar lavage fluid (BALF) of mice were detected. In addition, the correlation of MDSCs with the levels of IL-10 and IL-12 in the transplantation group was analyzed. The transplantation of tumor-derived MDSCs into asthmatic mice significantly improved airway remodeling, decreased MDSCs and the expression of IL-10, and significantly increased the expression of IL-12. Besides, we confirmed that IL-10 was positively correlated with MDSCs, while IL-12 was negatively correlated with MDSCs. The results indicated that tumor-derived MDSCs could reduce IL-10 level, increase the level of IL-12, and thus correct the Th1/Th2 imbalance in asthmatic mice. In summary, our results revealed that tumor-derived MDSCs could serve as a potential novel target for asthma therapy.

摘要

髓源性抑制细胞(MDSCs)是一组新发现的异质性髓源性免疫抑制细胞,在哮喘进展中起重要作用,然而,具体机制仍不清楚。我们之前的研究表明,在哮喘发作期间,MDSCs的积累和血清白细胞介素(IL)-10水平升高,而IL-12水平降低。本研究旨在探讨肿瘤来源的MDSCs是否能通过调节IL-10和IL-12的分泌来抑制哮喘小鼠的气道重塑。为了进行我们的研究,我们建立了乳腺癌小鼠模型,并将从乳腺癌小鼠模型中提取的MDSCs注射到卵清蛋白(OVA)诱导的哮喘小鼠模型中。然后,分析小鼠的哮喘气道重塑情况,并检测小鼠血清和支气管肺泡灌洗液(BALF)中IL-10和IL-12的水平。此外,分析了移植组中MDSCs与IL-10和IL-12水平的相关性。将肿瘤来源的MDSCs移植到哮喘小鼠中可显著改善气道重塑,降低MDSCs和IL-10的表达,并显著增加IL-12的表达。此外,我们证实IL-10与MDSCs呈正相关,而IL-12与MDSCs呈负相关。结果表明,肿瘤来源的MDSCs可降低IL-10水平,提高IL-12水平,并由此纠正哮喘小鼠的Th1/Th2失衡。总之,我们的结果表明肿瘤来源的MDSCs可能成为哮喘治疗的潜在新靶点。

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Eur Ann Allergy Clin Immunol. 2018 May;50(3):108-116. doi: 10.23822/EurAnnACI.1764-1489.46. Epub 2017 Nov 28.
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Trajectories of lung function during childhood.儿童时期肺功能的变化轨迹。
Am J Respir Crit Care Med. 2014 May 1;189(9):1101-9. doi: 10.1164/rccm.201309-1700OC.

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