[Zfp335 regulates the proportion of effector Treg and tumor immunity].

细胞与分子免疫学杂志 Pub Date : 2025-05-01
Xiaonan Shen, Wenhua Li, Xiaoxuan Jia, Biao Yang, Xin Wang, Haiyan Liu, Anjun Jiao, Lei Lei, Xiaofeng Yang, Baojun Zhang
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Abstract

Objective Zinc finger protein 335 (Zfp335) plays a crucial role in the early development of thymic T cells and the differentiation of peripheral T cell subpopulations. The objective of this study is to investigate the role and underlying mechanisms of Zfp335 in the regulation of regulatory T cell (Treg) within tumor immunity. Methods The Zfp335 gene was specifically knocked out in Treg using tamoxifen (Zfp335fl/fl FOXP3creERT2), and the MC38 tumor model was established. On the 7th day after tumor inoculation, tumor size was observed and measured. Tumor size was monitored and recorded daily starting from day 7 post-inoculation. On day 12, tumors were harvested, and the proportions of CD4+ T cells, CD8+ T cells, and Treg were analyzed by flow cytometry. Additionally, the mitochondrial function of effector regulatory T cell (eTreg) was assessed. Results From day 10 post-tumor inoculation, tumor volume in the Zfp335CKO group was significantly reduced compared to that of the wild-type (WT) group. Furthermore, the infiltration of CD4+ and CD8+ T cells, along with their respective effector cells, was significantly higher in the Zfp335CKO group than in the WT group. The proportions of CD4+ and CD8+ T cells producing interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) were also significantly increased in the Zfp335CKO group compared to that of the WT group. In addition, the percentage of CD8+ T cells secreting granzyme B (GzmB) was significantly higher in the Zfp335CKO group than that in the WT group. In contrast, the proportion of Treg and inducible T cell co-stimulator (ICOS)+ Treg in the Zfp335CKO group was significantly lower than that in the WT group. Finally, the expression level of Mitotracker Deep Red in eTreg from the Zfp335CKO group was significantly reduced compared to that in the WT group. Conclusion During tumorigenesis, the specific deletion of Zfp335 impairs Treg activation, which is related to decreased mitochondrial function in eTreg. In Zfp335CKO mice. Tumors exhibit increased infiltration of effector T cells, accompanied by elevated levels of cytotoxic cytokines, ultimately enhancing resistance to tumor progression.

[Zfp335调节效应Treg和肿瘤免疫的比例]。
目的锌指蛋白335 (Zfp335)在胸腺T细胞早期发育和外周血T细胞亚群分化过程中发挥重要作用。本研究的目的是探讨Zfp335在肿瘤免疫中调控调节性T细胞(Treg)的作用及其潜在机制。方法采用他莫昔芬特异性敲除Treg中的Zfp335基因(Zfp335fl/fl FOXP3creERT2),建立MC38肿瘤模型。接种肿瘤后第7天,观察并测定肿瘤大小。从接种后第7天开始,每天监测和记录肿瘤大小。第12天,取肿瘤,流式细胞术检测CD4+ T细胞、CD8+ T细胞和Treg细胞的比例。此外,我们还评估了效应调节性T细胞(eTreg)的线粒体功能。结果从肿瘤接种后第10天起,与野生型(WT)组相比,Zfp335CKO组的肿瘤体积显著减小。此外,Zfp335CKO组CD4+和CD8+ T细胞及其各自的效应细胞的浸润量明显高于WT组。与WT组相比,Zfp335CKO组CD4+和CD8+ T细胞产生干扰素-γ (IFN-γ)和肿瘤坏死因子-α (TNF-α)的比例也显著增加。此外,Zfp335CKO组分泌颗粒酶B (granzyme B, GzmB)的CD8+ T细胞比例显著高于WT组。相比之下,Zfp335CKO组Treg和ICOS + Treg的比例显著低于WT组。最后,与WT组相比,Zfp335CKO组eTreg中Mitotracker Deep Red的表达水平显著降低。结论在肿瘤发生过程中,Zfp335的特异性缺失损害了Treg的激活,这与eTreg线粒体功能下降有关。在Zfp335CKO小鼠中。肿瘤表现出效应T细胞浸润增加,伴随着细胞毒性细胞因子水平升高,最终增强对肿瘤进展的抵抗力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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