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Patients with radiation enteritis present regulatory T cell impairment associated with CTLA-4.
Immunologic Research ( IF 3.3 ) Pub Date : 2020-07-03 , DOI: 10.1007/s12026-020-09142-8
Xufeng Gong 1 , Genhua Yu 1 , Zongchang Song 2 , Shuqi Huang 3 , Yan Hou 1 , Ning Wang 1 , Wei Zhao 1 , Jingjing Ouyang 1 , Zhengzhou Gu 1 , Haili Hu 1 , Lei Fei 1 , Aixia Fu 4 , Jingping Xia 5 , Yuehua Ding 6
Affiliation  

Radiation enteritis is one of the most common side effects of ionizing radiation in patients with pelvic cancers. Increasing amounts of evidence indicate that pro-inflammatory responses significantly contribute to the development of radiation enteritis. In this study, we investigated the association between T regulatory (Treg) cells and the risk of developing radiation enteritis in cervical cancer patients. The following observations were made. First, the frequencies of CD25hiFoxp3+ Treg cells were significantly lower in patients with radiation enteritis than in both healthy subjects and cervical cancer patients without radiation enteritis. Also, patients with the more severe grade 3 enteritis presented significantly lower Treg levels than patients with the more common grade 1 enteritis. Second, the expression of several molecules associated with Treg function, including CTLA-4, IL-10, TGF-β, and perforin, was significantly lower in patients with radiation enteritis than in healthy subjects. In patients without radiation enteritis, however, only CTLA-4, but not other Treg-associated suppressive molecules, was reduced in Treg cells. Third, Treg cells can markedly suppress CD8 T cell proliferation, but in patients with radiation enteritis, this function of Treg cells was significantly impaired, in a manner that was associated with lower CTLA-4 expression. Overall, these data suggest that the frequency and function of Treg cells is negatively associated with the risk of developing enteritis following radiation. In clinical practice, the characteristics of Treg cells may be considered to evaluate the risk of developing enteritis if the cancer patient is receiving ionizing radiation.



中文翻译:

放射性肠炎患者表现出与 CTLA-4 相关的调节性 T 细胞损伤。

放射性肠炎是盆腔癌患者电离辐射最常见的副作用之一。越来越多的证据表明,促炎反应显着促进了放射性肠炎的发展。在这项研究中,我们调查了 T 调节 (Treg) 细胞与宫颈癌患者发生放射性肠炎的风险之间的关联。进行了以下观察。一、CD25 hi Foxp3 +的频率放射性肠炎患者的 Treg 细胞显着低于健康受试者和没有放射性肠炎的宫颈癌患者。此外,与更常见的 1 级肠炎患者相比,更严重的 3 级肠炎患者的 Treg 水平显着降低。其次,放射性肠炎患者中与 Treg 功能相关的几种分子,包括 CTLA-4、IL-10、TGF-β 和穿孔素的表达显着低于健康受试者。然而,在没有放射性肠炎的患者中,Treg 细胞中只有 CTLA-4 减少,而其他 Treg 相关抑制分子没有减少。第三,Treg细胞可以显着抑制CD8 T细胞增殖,但在放射性肠炎患者中,Treg细胞的这种功能明显受损,以与较低的 CTLA-4 表达相关的方式。总体而言,这些数据表明 Treg 细胞的频率和功能与辐射后发生肠炎的风险呈负相关。在临床实践中,如果癌症患者接受电离辐射,可以考虑Treg细胞的特征来评估发生肠炎的风险。

更新日期:2020-07-03
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